Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.58032293
Smad 3 interacted indirectly with Sp 1 through its association with Smad 2 and / or Smad 4 , and bound directly to the p 15 ( Ink4B ) promoter . 0.58032293^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :1.3685777
The FM differs from the SIM since it discriminates between Smad 2 and Smad 3 , and moreover only binds phosphorylated Smad 2 in the context of activated Smad complexes . 1.3685777^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
When expressed in wing imaginal disks , hSmad 2 induced oversize wings while hSmad 3 induced cell death . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activation of transforming growth factor beta ( TGF beta ) and activin receptors leads to phosphorylation of Sma and Mad related protein 2 ( Smad 2 ) and Smad 3 , which function as transcription factors to regulate gene expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
After activation of TGF beta receptors , Smad 2 and Smad 3 become phosphorylated and form heteromeric complexes with Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Studies in which the mammalian Smad homologs were transiently overexpressed in cultured cells have implicated Smad 2 in TGF beta signaling , but the physiological relevance of the Smad 3 protein in signaling by TGF beta receptors has not been established . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activation by transforming growth factor beta ( TGF beta ) / activin receptors leads to phosphorylation of Smad 2 ( Sma and Mad related protein 2 ) and Smad 3 , which function as transcription factors to regulate gene expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 1 and Smad 2 have been shown to mimic the effects of BMP and activin , respectively , both in Xenopus and in mammalian cells , whereas Smad 3 ( a close homologue of Smad 2 ) and the related protein DPC 4 , a tumour suppressor gene product , mediate TGF beta actions . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The finding that Smad 4 , unlike Smad 3 , does not interact with the TGF beta receptor , coupled with the distinct structural features of Smad 4 , raises the possibility that Smad 4 cooperates not only with Smad 3 , but also with Smad 1 and Smad 2 to mediate signaling by TGF beta family members . ^^^ In addition , Smad 4 synergized Smad 2 , as it does with Smad 3 , to induce gene expression from the promoter for plasminogen activator inhibitor 1 . ^^^ CONCLUSIONS : Our observations indicate that Smad 4 cooperates with Smad 1 , Smad 2 and Smad 3 to act as a common mediator of signaling by TGF beta related factors , and provide a mechanism that explains the dominant negative interference with receptor signaling that results from expression of the naturally occurring Smad4 / DPC 4 truncation mutant . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 1 is regulated in this fashion by BMP receptors , and Smad 2 and Smad 3 by TGF beta and activin receptors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta receptor mediated signalling through Smad 2 , Smad 3 and Smad 4 . ^^^ Smad 2 and Smad 3 are structurally highly similar and mediate TGF beta signals . ^^^ Here we show that Smad 2 and Smad 3 interacted with the kinase deficient TGF beta type 1 receptor ( TbetaR ) 1 after it was phosphorylated by TbetaR 2 kinase . ^^^ TGF beta 1 induced phosphorylation of Smad 2 and Smad 3 in Mv1Lu mink lung epithelial cells . ^^^ In addition , we observed TbetaR activation dependent interaction between Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 1 , Smad 2 , Smad 3 and Smad 5 are ligand specific : Smadl and Smad 5 transduce signals from bone morphogenetic proteins , and Smad 2 and Smad 3 mediate signalling by TGF beta and activin , whereas Smad 4 acts as a common signalling component . ^^^ Smad 6 interferes with the phosphorylation of Smad 2 and the subsequent heteromerization with Smad 4 , but does not inhibit the activity of Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad family members ( Smad 1 , Smad 2 , Smad 3 and Smad 4 ) are expressed in the cultured retinal pigmant epithelial cell line ( D 407 ) , in which TGF beta and activin A stimulate the translocation of Smad 2 , but not Smad 1 into nuclei , whereas bone morphogenetic protein ( BMP ) stimulates that of Smad 1 , but not Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Abrogation of Smad 3 and Smad 2 or of Smad 4 gene expression positively regulates murine embryonic lung branching morphogenesis in culture . ^^^ Antisense oligodeoxynucleotides were designed to attenuate Smad 3 and Smad 2 gene expression in embryonic ( E 11 ) mouse lungs over 4 days in culture . ^^^ Endogenous Smad 3 and Smad 2 mRNA levels were suppressed by 97 and 91 % , respectively , in cultured embryonic lungs when antisense oligodeoxynucleotide ( 40 microM ) to Smad was added , compared to scrambled and sense sequence controls . ^^^ The corresponding Smad 3 and Smad 2 protein amounts were also decreased respectively by 86 and 90 % in lungs treated with Smad 3 and Smad 2 antisense oligodeoxynucleotide . ^^^ Thus , inhibition of endogenous Smad 3 and Smad 2 gene expression resulted in stimulation of embryonic lung branching similar to that caused by inhibition of TGF beta type 2 receptor expression and signaling ( J . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 mediate TGF beta signaling , whereas Smad 1 and Smad 5 transduce bone morphogenetic protein ( BMP ) signals . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The vertebrate members of the MAD related family , termed Smad 2 and Smad 3 , interact specifically with the TGF beta type 1 receptor and are phosphorylated on the last two serines of a conserved C terminal SSXS motif . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 , and Smad 4 , which are involved in TGF beta signaling , were expressed in the retinoblastoma cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We have also shown that in HaCaT cells , activin A induced the phosphorylation of Smad 3 and , to a lesser extent , of Smad 2 . ^^^ On the other hand , TGF beta induced an efficient phosphorylation of both Smad 2 and Smad 3 . ^^^ Activin A preferentially induced the nuclear translocation of Smad 3 in HaCaT cells , whereas TGF beta strongly induced the nuclear translocation of Smad 2 , as well as other Smads . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Upon TGF beta receptor activation , Smad 2 and Smad 3 become phosphorylated and form heteromeric complexes with Smad 4 . ^^^ Furthermore , bacterially expressed Smad 3 and Smad 4 proteins , but not Smad 1 nor Smad 2 protein , bind directly to this sequence in vitro . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF Beta RI phosphorylates the downstream effectors Smad 2 and Smad 3 , leading to their translocation into the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activated TGF betaRI phosphorylates two downstream effectors , Smad 2 and Smad 3 , leading to their translocation into the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 form homo oligomers upon phosphorylation by the constitutively active TGF beta type 1 receptor , and this oligomerization does not require Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 positively and negatively regulate TGF beta dependent transcription through the forkhead DNA binding protein FAST 2 . ^^^ Smad 3 is closely related to Smad 2 but suppresses activation of the gsc promoter . ^^^ Thus , we describe a mechanism whereby Smad 2 and Smad 3 positively and negatively regulate a TGF beta / activin target gene . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Type 1 receptors , in turn , phosphorylate cytoplasmic transcriptional activator proteins Smad 2 and Smad 3 , inducing their translocation to the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFbeta transduces its signal to the interior of the cell via Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The ECM production stimulation by TGF beta or CA TbetaR 1 was accelerated by the overexpression of Smad 2 , Smad 3 , and / or Smad 4 and inhibited by that of Smad 7 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are specific mediators of TGF beta and activin , while Smadl and Smad 5 are involved in bone morphogenetic protein 2 ( BMP 2 ) and BMP 4 signaling . ^^^ Smad 1 , Smad 5 , and Smad 8 , but not Smad 2 and Smad 3 , were found to stably interact with the kinase deficient BMPR IB after it was phosphorylated by the BMPR 2 kinase . ^^^ In ROB C 26 cells , which express Smad 2 , Smad 3 , Smad 4 , and Smad 5 , OP 1 was found to stimulate the phosphorylation of Smad 5 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta and activin induce the phosphorylation and activation of Smad 2 and Smad 3 , but how these proteins stimulate gene transcription is poorly understood . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A single missense mutant of Smad 3 inhibits activation of both Smad 2 and Smad 3 , and has a dominant negative effect on TGF beta signals . ^^^ A missense mutation of Smad 2 identified in cancer cells was reconstructed on the corresponding residue of Smad 3 . ^^^ This mutant , Smad3D407E , was not phosphorylated by the constitutively active form of type 1 receptor for transforming growth factor beta ( TGF beta ) , and inhibited the phosphorylation of co expressed wild type Smad 2 and Smad 3 . ^^^ These findings showed that a single missense mutation in Smad 3 could specifically block TGF beta signals by preventing activation of both Smad 2 and Smad3 . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transient overexpression of Smad 3 and Smad 4 , but not Smad 1 or Smad 2 , caused trans activation of a CAT reporter gene driven by a 772 bp segment of the human COL1A2 promoter containing putative TGF beta response elements . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Indeed , soon after their association with the activin receptor , Smad 2 and Smad 3 are released into the cytoplasm where they interact with the common partner Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Two highly homologous molecules , Smad 2 and Smad 3 , have so far been identified as receptor activated Smads for TGF beta signaling and have become the focus of intensive studies . ^^^ In the present study , we show that the expression of Smad 3 , but not its close relative , Smad 2 , is down regulated by TGF beta mediated signals themselves in human lung epithelial cells . ^^^ Apoptotic cell death could also be induced by forced expression of Smad 2 in the presence of TGF beta , but less efficiently than by that of Smad 3 . ^^^ These findings clearly define the distinctions between Smad 2 and Smad 3 for the first time in that a qualitative difference was observed with regard to the regulation of their expression in response to TGF beta , while Smad 2 and Smad 3 appeared to have quantitatively different capabilities regarding the induction of apoptotic cell death in human lung epithelial cells . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Overexpression of Smad 2 gene enhanced endogenous Smad 4 gene expression in both ROS17 / 2 . 8 and PRC cells , while Smad 3 levels were not altered . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
E1A inhibited this enhancement , and the inhibition required its ability to bind p300 / CBP . p 300 and Smad 3 , as well as Smad 2 , interacted in vivo in a ligand dependent manner . ^^^ CONCLUSION : p 300 interacted with Smad 2 and Smad 3 in a ligand dependent manner , and enhanced the transactivation by Smads . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Electrophoretic mobility shift assays using recombinant glutathione S transferase SMAD fusion proteins indicate that both SMAD 4 and C terminally truncated SMAD 3 , but not SMAD 2 , can bind the COL7A1 SBS . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We now identify SARA ( for Smad anchor for receptor activation ) , a FYVE domain protein that interacts directly with Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Comparison with wild type Smad 2 and Smad 3 . ^^^ Here , we studied the function of Smad2Deltaexon3 and compared it with those of wild type Smad 2 containing exon 3 ( Smad 2 ( wt ) ) and Smad 3 . ^^^ When transcriptional activity was measured using the p3TP lux construct , Smad2Deltaexon3 was more potent than Smad 2 ( wt ) , and had activity similar to Smad 3 . ^^^ Transcriptional activation of the activin responsive element ( ARE ) of Mix . 2 gene promoter by Smad2Deltaexon3 was also similar to that by Smad 3 , and slightly less potent than that by Smad 2 ( wt ) . ^^^ Phosphorylation by the activated transforming growth factor beta type 1 receptor and heteromer formation with Smad 4 occurred to similar extents in Smad2Deltaexon3 , Smad 2 ( wt ) , and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 protein was abundantly present in U 178 MG , U 343 MG , and U 343 MGa 35L , while Smad 3 was readily detectable in U 178 MG , U 343 MG , U 343 MGa 35L and U 251 MG AgCl 1 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signaling is initiated when the type 1 receptor phosphorylates the SMAD proteins , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFB receptor activation results in SMAD 2 and SMAD 3 phosphorylation , which then form heteromeric complexes with SMAD 4 . ^^^ Inhibitory SMADs , SMAD 6 and SMAD 7 , can prevent TGFB signaling by interacting either with the receptor or with SMAD 2 and SMAD 3 . ^^^ The encoding sequences for these proteins are organized in two gene clusters , one at 18q21 ( SMAD 2 , SMAD 4 , and SMAD 7 ) and the other at 15q21 22 ( SMAD 3 and SMAD 6 ) . ^^^ Losses of 15q and 18q material are frequent in pancreatic carcinomas , and in order to map the extent of 15q and 18q deletions and to investigate further the involvement of SMAD 4 and the possible function of SMAD 2 and SMAD 3 as tumor suppressor genes in pancreatic carcinoma , we performed loss of heterozygosity studies as well as mutation and expression analyses of SMAD 4 , SMAD 2 , and SMAD 3 in 13 low passage cell lines from 12 pancreatic carcinoma patients . ^^^ One tumor with homozygous loss of SMAD 4 was detected , and mutations of this gene were found in four of the 12 carcinomas ; no SMAD 2 or SMAD 3 inactivating genomic alterations were found . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The MH 1 domains of smad 2 and smad 3 are involved in the regulation of the ALK 7 signals . ^^^ The constitutively active form of ALK 7 , ALK 7 ( T194D ) , activated Smad 3 and a chimeric Smad protein , Smad 3 2 , containing the MH 1 domain of Smad 3 and the MH 2 domain of Smad 2 , and translocated them to nuclei and then induced activation of the human PAI 1 promoter . ^^^ However , neither Smad 2 nor Smad 2 3 protein , containing the MH 1 domain of Smad 2 and the MH 2 domain of Smad 3 were activated . ^^^ These results indicate that the ALK 7 signal regulates nuclear localization and activation of Smad 2 and Smad 3 , and the MH 1 domain of Smad 2 has inhibitory effects on the nuclear localization . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
IGFBP 3 did not stimulate the cellular phosphorylation of Smad 2 and Smad 3 , key transducers of the transforming growth factor beta type I / type 2 receptor ( TbetaR I . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 mRNAs were detected in all 6 cell lines examined , whereas Smad 4 mRNA was not detected in MDA MB 468 cells , which are known to harbor a homozygous deletion of the Smad 4 gene . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Upon phosphorylation by the TGFbeta receptors , Smad 2 and Smad 3 homoligomerize and heteroligomerize with Smad 4 , translocate to the nucleus and activate transcription of TGFbeta responsive genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The predicted amino acid ( aa ) sequences of mouse Smad 3 showed a high homology with human Smad 3 ( 99 . 3 % ) and mouse Smad 2 ( 85 . 4 % ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 , Smad 4 , Smad 6 and Smad 7 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Twenty one Smad 4 mutations and one Smad 2 mutation were detected , whereas mutation of Smad 3 , 6 and 7 genes was not detected . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta 1 mediated receptor activation induces phosphorylation of Smad 2 and Smad 3 , which form complexes with Smad 4 , that translocate to the nucleus to regulate transcription of target genes . ^^^ The staining for Smad 2 , P Smad 2 , Smad 3 , Smad 4 , and Smad 7 was nuclear in some cells and was present in areas with a large number of apoptotic cells identified by various morphological criteria , formation of apoptotic bodies and , in adjacent sections , by terminal deoxynucleotidyl transferase mediated nick end labeling assay . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RESULTS : The mRNAs for Smad 2 and Smad 4 were abundantly expressed whereas the expression of mRNA for Smad 1 and Smad 3 was very low . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We found increased expression of receptor activated Smads in a fraction of the tumor cells , while no immunostaining for Smad 2 , Smad 3 or Smad 5 and only occasional staining for Smad1 / 8 was found in epithelial mucosa of normal colon . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A short amino acid sequence in MH 1 domain is responsible for functional differences between Smad 2 and Smad 3 . ^^^ TGFbeta binding to heteromeric complexes of transmembrane Ser / Thr kinases induces Smad 2 and Smad 3 phosphorylation on their C terminus residues . ^^^ Even if they share 92 % identity , the two TGFbeta / restricted Smad 2 and Smad 3 are not functionally equivalent . ^^^ As we have previously shown , Smad 3 acts as a transcription factor by binding to a TGFbeta responsive sequence termed CAGA box whereas Smad 2 does not . ^^^ Smad 2 differs from Smad 3 mainly in the N terminal MH 1 domain where it contains two additional stretches of amino acids that are lacking in Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we report that oncogenic Ras inhibits TGFbeta signaling in mammary and lung epithelial cells by negatively regulating the TGFbeta mediators Smad 2 and Smad 3 . ^^^ Oncogenically activated Ras inhibits the TGFbeta induced nuclear accumulation of Smad 2 and Smad 3 and Smad dependent transcription . ^^^ Ras acting via Erk MAP kinases causes phosphorylation of Smad 2 and Smad 3 at specific sites in the region linking the DNA binding domain and the transcriptional activation domain . ^^^ EGF , which is weaker than oncogenic mutations at activating Ras , induces a less extensive phosphorylation and cytoplasmic retention of Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RESULTS : Here we report the identification of dSmad 2 , a new Drosophila Smad which is most related to the activin / TGFbeta pathway Smads , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We found expression of all TbetaR ' s ( type 1 , 2 and 3 ) and SMAD proteins analysed ( Smad 2 , Smad 3 , Smad 4 , Smad 6 and Smad 7 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Both TGF beta 1 and activin A , but not BMP 7 , increased the phosphorylation of Smad 2 , induced nuclear translocation of Smad 2 , Smad 3 , and Smad 4 , and inhibited thyrocyte cell growth as well as TSH stimulated cAMP response . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
This complex contains Smad 2 or Smad 3 , Smad 4 , and a novel forkhead transcription factor , FAST 1 , and binds to an enhancer ( activin responsive element ; ARE ) that confers activin regulation of Mix . 2 transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
On phosphorylation and activation by the active TGFbeta receptor complex , Smad 2 and Smad 3 form hetero oligomers with Smad 4 and translocate into the nucleus , where they interact with different cellular partners , bind to DNA , regulate transcription of various downstream response genes , and cross talk with other signaling pathways . ^^^ Here we show that a nuclear oncoprotein , Ski , can interact directly with Smad 2 , Smad 3 , and Smad 4 on a TGFbeta responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N CoR and possibly its associated histone deacetylase complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activated TbetaRI then mediates TGF beta signals by inducing the phosphorylation of Smad 2 and / or Smad 3 , which separately hetetorodimerize with Smad 4 and translocate to the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 1 and Smad 5 mediate intracellular signaling of bone morphogenetic protein ( BMP ) , whereas Smad 2 and Smad 3 transduce TGF beta signaling . ^^^ The TGF beta / activin restricted Smads were also expressed in a nearly complementary fashion ; Smad 2 was strongly expressed in proliferating chondrocytes , whereas Smad 3 was strongly observed in maturing chondrocytes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To study the possibility that germline mutations in other genes encoding different components of the TGF beta signaling pathway may be present in these JP patients , mutation analyses of the SMAD 2 , SMAD 3 , and SMAD 7 genes were also performed . ^^^ Our results confirm that SMAD 4 is a gene predisposing to JP and suggest the existence of further JP loci other than the SMAD 2 , SMAD 3 , or SMAD 7 genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Screening SMAD 1 , SMAD 2 , SMAD 3 , and SMAD 5 for germline mutations in juvenile polyposis syndrome . ^^^ Other members of the SMAD family are excellent candidates for JPS , especially SMAD 2 ( which , like SMAD 4 , is mutated somatically in colorectal cancers ) , SMAD 3 ( which causes colorectal cancer when `` knocked out ' ' in mice ) , SMAD 5 , and SMAD 1 . ^^^ METHODS : SMAD 1 , SMAD 2 , SMAD 3 , and SMAD 5 were screened for germline mutations in 30 patients with JPS and without SMAD 4 mutations . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signals through its cell surface receptor serine kinases that phosphorylate Smad 2 or Smad 3 proteins . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 4 acts as a cofactor that binds transforming growth factor beta ( TGF beta ) receptor activated Smad 2 and Smad 3 generating transcriptional complexes . ^^^ Co transfection into SW480 . 7 cells of Smad 4 together with a Ras phosphorylation resistant Smad 3 ( but not with wild type Smad 2 , Smad 3 , adenomatous polyposis coli ( APC ) , or TGF beta type 2 receptor ) restored the TGF beta antiproliferative response . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Consistent with these findings , TGF ( beta ) 1 induced the nuclear accumulation of Smad 2 and / or Smad 3 . ^^^ On the other hand , infections with low level CA ALK 5 , which alone did not result in transdifferentiation , together with Smad 2 and Smad 4 , or with Smad 3 and Smad 4 led to transdifferentiation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A missense mutation of Smad 2 identified in colorectal and lung cancers was introduced to Smad 3 . ^^^ The mutant , Smad 3 ( DE ) , blocked the activation of wild type Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
These experiments have shown that Smad 2 and Smad 4 are needed for gastrulation , Smad 5 for angiogenesis , and Smad 3 for establishment of the mucosal immune response and proper development of the skeleton . ^^^ These include gastrulation and craniofacial defects for Smad 2 , accelerated wound healing for Smad 3 , and the incidence of gastric cancer for Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Phosphorylation of Smad 2 and Smad 3 was determined by both phospholabeling and immunoblot . ^^^ RESULTS : Cultured human mesangial cells express Smad 2 , Smad 3 , and Smad 4 proteins . ^^^ TGF beta 1 down regulated Smad 3 mRNA and protein expression , respectively , after 4 and 24 hours of treatment , whereas Smad 2 and Smad 4 were less affected . ^^^ Both Smad 2 and Smad 3 were phosphorylated in response to TGF beta 1 beginning at 5 minutes , with maximal phosphorylation at 15 minutes , and decreasing phosphorylation by 2 hours . ^^^ CONCLUSIONS : Smad 2 , Smad 3 , and Smad 4 are present and activated by TGF beta 1 in human mesangial cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transcriptional regulation by transforming growth factor beta and activin is mediated by interaction of Smad 2 and Smad 3 with specific transcription factors and / or DNA elements . ^^^ However , Smad 3 behaves differently from Smad 2 in regulating transcription by a winged helix transcription factor , FAST 2 , on an activin responsive element ( ARE ) in the Xenopus Mix . 2 promoter . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we show that MDM 2 and the structurally related protein MDMX can inhibit the transcriptional activity of ectopically expressed SMAD 1 , SMAD 2 , SMAD 3 , and SMAD 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Both Smad 3 and its closely related homolog Smad 2 act as latent nuclear transcriptional activators and mediate intracellular signaling by TGF betas and activin , each of which regulates cellular functions pivotal to cutaneous wound healing . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Electrophoretic mobility shift assays using oligonucleotide probes demonstrated that TGF beta rapidly induced the binding of an endogenous SBE binding complex ( SBC ) containing Smad 2 , Smad 3 , and Smad 4 . ^^^ Transfection assays in mouse embryonic fibroblasts ( MEFs ) , with targeted deletions of either Smad 2 or Smad 3 , and the Smad 4 deficient cell line MD MBA 468 revealed that both Smad 3 and Smad 4 , but not Smad 2 , were absolutely required for induction of the Smad 7 promoter reporter gene by TGF beta . ^^^ Furthermore , the TGF beta inducible SBE binding complex was diminished in Smad 2 deficient MEFs when compared with wild type MEFs and not detectable in Smad 3 deficient MEFs and MD MBA 468 cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Moreover , STRAP stabilizes the association between Smad 7 and the activated receptor , thus assisting Smad 7 in preventing Smad 2 and Smad 3 access to the receptor . ^^^ STRAP interacts with Smad 2 and Smad 3 but does not cooperate functionally with these Smads to transactivate TGF beta dependent transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Cloning and characterization of zebrafish smad 2 , smad 3 and smad 4 . smad genes encode transcription factors involved in the signal transduction of members of the TGFbeta superfamily . ^^^ We report here the cloning , characterization and genomic mapping of smad 2 , smad 3 and smad 4 from the zebrafish , Danio rerio . ^^^ Zygotic expression is weak and ubiquitous in the case of smad 2 , and strong and ubiquitious in the case of smad 4 , while smad 3 shows a spatially restricted zygotic expression pattern . ^^^ These data suggest that Smad 2 acts as a mediator of Nodal signals during zebrafish midline signaling , while Smad 3 might be involved in later steps of eye field separation . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction ( RT PCR ) analysis demonstrated that each cell line expresses both type 1 and type 2 activin receptors and signaling molecules for activin , Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 7 was recently shown to antagonize TGF beta induced activation of signal transducing Smad 2 and Smad 3 proteins . ^^^ By immunocytochemistry , Smad 7 protein was co localized with both Smad 2 and Smad 3 in distal bronchial epithelial cells , supporting the concept that Smad 7 inhibits TGF beta signaling by competing locally with Smad 2 and Smad 3 for TGF beta receptor complex binding during lung morphogenesis . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We investigated the production of TGF beta 1 , the biological effects of TGF beta and neutralizing antibody on HCC cells , activation of Smad 2 , Smad 3 , and Smad 4 , induction of antagonistic Smads ( Smad 6 and Smad 7 ) , and promoter activities of two target genes , plasminogen activator inhibitor type 1 ( PAI 1 ) and p15INK4B . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Mutation analysis of SMAD 2 , SMAD 3 , and SMAD 4 genes in hereditary non polyposis colorectal . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Overexpression of Smad 2 and Smad 3 transactivated the PDGF B promoter in a synergistic manner . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Through the use of electrophoretic mobility shift assays , we showed the presence of Smad 2 , Smad 3 , and Smad 4 in complexes binding to the Smad binding element . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Whereas the negative growth regulation by TGF beta 1 was completely inhibited by dominant negative Smad 2 , Smad 3 , or Smad 4 , its mitogenic effect was not affected , suggesting that this action is Smad independent . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
For example , use of cells deficient in Smad 2 for biochemical and cell biological assays could give a better view of the function of Smad 3 . ^^^ Smad 3 deficient mice already demonstrate that there is a clear difference between Smad 2 and Smad 3 during development . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Stable overexpression of Smad 2 or Smad 3 inhibited differentiation and dominant negative inhibition of Smad 3 function , but not Smad 2 function , enhanced adipogenesis . ^^^ Our results indicate that endogenous TGF beta signaling regulates the rate of adipogenesis , and that Smad 2 and Smad 3 have distinct functions in this endogenous control of differentiation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta induces the phosphorylation of Smad 2 and Smad 3 ( receptor activated Smads ) which associate with Smad 4 and translocate to the nucleus , where they regulate gene transcription [ 1 ] . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Ski acts as a co repressor with Smad 2 and Smad 3 to regulate the response to type beta transforming growth factor . ^^^ The results of the screen and subsequent co immunoprecipitation studies identified Smad 2 and Smad 3 , two transcriptional activators that mediate the type beta transforming growth factor ( TGF beta ) response , as Ski interacting proteins . ^^^ DNA binding assays showed that Ski , Smad 2 , Smad 3 , and Smad 4 form a complex with the Smad / Ski binding element GTCTAGAC ( SBE ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We analyzed the mRNA expression of TGF beta 1 , TGF beta 2 , TGF beta 3 , the TGF beta receptors type 1 ( TbetaR 1 ) and type 2 ( TbetaR 2 ) , Smad 2 , Smad 3 , and Smad 4 . mRNA expression of IL 10 and CD 95 ( FAS / APO 1 ) were also studied . ^^^ However , the mRNA expression of Smad 2 , Smad 3 , and Smad 4 was decreased in GBM . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RESULTS : TGFbeta produced little inhibition of DNA synthesis and did not activate a TGFbeta responsive reporter in pancreatic cancer cell lines . 125TGFbeta cross linking and RT PCR confirmed the presence of TGFbeta receptors and Smad 2 and Smad 3 transcripts . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Structural basis for the functional difference between Smad 2 and Smad 3 in FAST 2 ( forkhead activin signal transducer 2 ) mediated transcription . ^^^ Smad 2 and Smad 3 are signalling proteins that are involved in mediating the transcriptional regulation of target genes downstream of transforming growth factor beta and activin receptors . ^^^ Although they are structurally very similar , Smad 2 and Smad 3 have some functional differences in transducing signals for these receptors . ^^^ In FAST 2 ( forkhead activin signal transducer 2 ) mediated transcriptional regulation using the activin responsive element derived from Xenopus Mix . 2 promoter as a reporter , Smad 3 but not Smad 2 alone was able to stimulate the transcription . ^^^ In addition , Smad 3 was able to inhibit the transactivation of the promoter induced by co expression of Smad 2 , Smad 4 and an active activin type 1 receptor . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Several proteins , including transforming growth factor beta ( TGF beta ) receptor type 1 ( RI ) , TGF beta receptor type 2 ( RII ) , Smad 2 , Smad 3 , and Smad4 / DPC4 , have been identified in the transduction pathway of the tumor suppressor TGF beta . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activation of transforming growth factor beta ( TGF beta ) receptors triggers phosphorylation of Smad 2 and Smad 3 . ^^^ Unlike other Smads , Smad 7 inhibits phosphorylation of Smad 2 and Smad 3 , and its transcription is induced by TGF beta , suggesting a negative feedback loop . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To investigate this synergism , the phosphorylation of TGF beta signaling intermediates , Smad 2 and Smad 3 , was measured . ^^^ These data suggest that IGFBP 3 inhibitory signaling requires an active TGF beta signaling pathway and implicate Smad 2 and Smad 3 in IGFBP 3 signal transduction . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Consistent with this result , dominant negative interference with Smad 2 and Smad 3 function also inhibited TGF beta induced apoptosis . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We found Smad 2 and Smad 3 transcripts both broadly expressed in derivatives of the epiblast . ^^^ However , Smad 2 and not Smad 3 mRNA is expressed in the visceral endoderm , potentially explaining why the primary defect in Smad 2 mutant embryos originates in this cell population . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We demonstrate that Sp 1 physically and directly interacts with Smad 2 , Smad 3 , and weakly with Smad 4 via their amino terminal ( Mad Homology 1 ) domain . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Participation of Smad 2 , Smad 3 , and Smad 4 in transforming growth factor beta ( TGF beta ) induced activation of Smad 7 . ^^^ Performing electrophoretic mobility shift assay and cotransfection experiments , we were able to delineate DNA binding complexes and identified Smad 3 , Smad 4 , and Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In both yeast two hybrid and in vitro binding assays , we found that Smurf 2 could interact with receptor activated Smads ( R Smads ) , including Smad 1 , Smad 2 , and Smad 3 but not Smad 4 . ^^^ Ectopic expression of Smurf 2 was sufficient to reduce the steady state levels of Smad 1 and Smad 2 but not Smad 3 or Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta receptor phosphorylation of SMAD 2 or SMAD 3 causes their association with SMAD 4 and accumulation in the nucleus where the SMAD complex binds cofactors that determine the choice of target genes . ^^^ SMAD 2 is found mostly as monomer , whereas the closely related SMAD 3 exists in multiple oligomeric states . ^^^ In contrast to SMAD 2 and SMAD 3 , SMAD 4 in the basal state is found mostly as a homo oligomer , most likely a trimer . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
These results provide the first direct biochemical evidence that nodal signaling is mediated by both activin TGF beta pathway Smads , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Cam kinase 2 induces in vivo phosphorylation of Smad 2 and Smad 4 and , to a lesser extent , Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
However , we found no evidence in this system that ERK can significantly influence the function of Smad 2 , Smad 3 , and Smad 4 at the level of nuclear translocation , DNA binding , or transcriptional activation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Mutation analysis of transforming growth factor beta type 2 receptor , Smad 2 , Smad 3 and Smad 4 in esophageal squamous cell carcinoma . ^^^ We performed polymerase chain reaction single strand conformation polymorphism analysis of TGFbetaRII , Smad 2 , Smad 3 and Smad 4 genes and microsatellite assay in 20 esophageal squamous cell carcinomas ( ESCC ) . ^^^ No mutation was found in TGFbetaRII , Smad 2 , Smad 3 and Smad 4 genes . ^^^ These results suggest that mutation of TGFbetaRII , Smad 2 , Smad 3 and Smad 4 genes is a rare event in ESCC . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The stimulation of the expression of HAS 2 at the mRNA level by TGF beta was accelerated by the overexpression of Smad 2 , Smad 3 , and Smad 4 and inhibited by that of Smad 7 , all of which were confirmed to be involved in the signal transduction from TGF beta through HAS expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are downstream transforming growth factor beta ( TGF beta ) signaling molecules . ^^^ Upon phosphorylation by its type 1 receptor , Smad 2 or Smad 3 forms a complex with Smad 4 and translocates to the nucleus where the complex activates target gene transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
According to the current model , activated activin / TGFbeta receptors phosphorylate the carboxyl terminal serines of Smad 2 and Smad 3 ( SSMS COOH ) ; phosphorylated Smad2 / 3 oligomerizes with Smad 4 , translocates to the nucleus , and modulates transcription of defined genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta mediated activation of TGF beta type 1 receptor stimulates the phosphorylation of Smad 2 and Smad 3 and subsequent heteromeric complex formation with Smad 4 . ^^^ Moreover , Smad 2 and Smad 3 interacted with P / CAF upon TGF beta type 1 receptor activation in cultured mammalian cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
All these Smad 4 variants form complexes with activated Smad 2 and Smad 3 and are incorporated into DNA binding complexes with the transcription factor Fast 1 , regardless of the amount of linker they contain . ^^^ Endogenous Smad 2 and Smad 3 are completely unaffected by leptomycin B treatment , indicating that the nucleocytoplasmic shuttling is specific for Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Expression of activated ALK 7 in PC 12 cells resulted in activation of Smad 2 and Smad 3 , but not Smad 1 , as well as the mitogen activated protein kinases extracellular signal regulated kinase and c Jun N terminal kinase . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Ligand induced activation of TGF beta family receptors with intrinsic serine / threonine kinase activity trigger phosphorylation of receptor regulated Smads ( R Smads ) , whereas Smad 2 and Smad 3 are phosphorylated by TGF beta , and activin type 1 receptors , Smad 1 , Smad 5 and Smad 8 , act downstream of BMP type 1 receptors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To learn about the role of TGF beta in vivo , phenotypes of targeted mutations of molecules within the TGF beta signalling pathway , TGF beta 1 , beta 2 , beta 3 , TGF beta receptor ( TbetaR 2 ) and the signalling molecules SMAD 2 , SMAD 3 and SMAD 4 , are discussed in this review . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Wild type and dominant negative forms of Smad 3 had more pronounced effects than Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To this end , the expression of molecules in the pathway has been examined by immunocytochemistry ( TGFbeta , TGFbetaR 2 , SMAD 2 , SMAD 3 , SMAD 4 , and p 27 ) , backed up by a cell culture assay of TGFbeta mediated growth suppression , RT PCR for SMAD 4 , and loss of heterozygosity ( LOH ) on 3p22 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFbeta induction of CTGF is dependent on SMAD 3 and SMAD 4 but not SMAD 2 and is p 300 independent . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Moreover , Smad 2 or Smad 3 with Smad 4 enhanced the proteolytic pathway of p 57 ( Kip 2 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
At higher expression levels , Smurf 2 also decreases the protein levels of Smad 2 , but not Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are two cellular mediators of activin / TGF beta signaling , whereas Smad 7 is as an inducible , negative modulator of the pathway . ^^^ In alpha T 3 1 cells , which express endogenous follistatin mRNA , a follistatin luciferase reporter , rFS ( rin 3 ) Luc , was transcriptionally activated by activin A , or when cotransfected with a constitutively active ActRIB [ Alk 4 ( T > D ) ] , Smad 2 , or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Binding of TGF beta to its receptor induces phosphorylation of the Smad proteins Smad 2 and Smad 3 , which then form heteromeric complexes with Smad 4 , translocate to the nucleus , and activate gene transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Effects of short photoperiod on the expression of smad 2 and smad 3 mRNA in Syrian hamster testis . ^^^ The testicular localization and expression of Smad 2 and Smad 3 mRNA involved in the intracellular signal transduction of activin , inhibin and transforming growth factor beta ( TGF beta ) were examined under the influence of long and short photoperiod in Syrian hamsters ( Mesocricetus auratus ) . ^^^ In situ hybridization detected both Smad 2 and Smad 3 mRNA in spermatogonia and premeiotic spermatocytes in the active testis exposed to a long photoperiod , as well as in the regressed testis exposed to a short photoperiod . ^^^ Northern blots showed that Smad 2 mRNA was expressed at all stages over long and short photoperiods , whereas Smad 3 mRNA was expressed at high levels in the photoperiod induced regressed testis . ^^^ The photoperiodic condition would change the balance between Smad 2 and Smad 3 transcripts in the testis . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Immunofluorescence studies revealed that , in contrast to Smad 2 that translocated from the cytoplasm to the nucleus upon TGF beta treatment , Smad 3 and Smad 4 were present in the nucleus irrespective of ligand stimulation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Functional characterization of transforming growth factor beta signaling in Smad 2 and Smad 3 deficient fibroblasts . ^^^ A prominent pathway of transforming growth factor ( TGF ) beta signaling involves receptor dependent phosphorylation of Smad 2 and Smad 3 , which then translocate to the nucleus to activate transcription of target genes . ^^^ To investigate the relative importance of these two Smad proteins in TGF beta 1 signal transduction , we have utilized a loss of function approach , based on analysis of the effects of TGF beta 1 on fibroblasts derived from mouse embryos deficient in Smad 2 ( S2KO ) or Smad 3 ( S3KO ) . ^^^ Lack of Smad 2 or Smad 3 expression did not affect TGF beta 1 induced fibronectin synthesis but resulted in markedly suppressed induction of plasminogen activator inhibitor 1 by TGF beta 1 . ^^^ Moreover , TGF beta 1 mediated induction of matrix metalloproteinase 2 was selectively dependent on Smad 2 , whereas induction of c fos , Smad 7 , and TGF beta 1 autoinduction relied on expression of Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 both associate with the c Ski and Sno oncoproteins to repress transcription of Smad target genes via recruitment of a nuclear corepressor complex . ^^^ SKIP interacted with Smad 2 and Smad 3 proteins in vivo in yeast and in mammalian cells through a region of SKIP between amino acids 201 333 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In contrast , the unique insert of exon 3 in the N terminal domain of Smad 2 prevents its association with importin beta 1 . 3 ) Nuclear import of Smad 3 in vivo requires the action of the Ran GTPase , which mediates release of Smad 3 from the complex with importin beta 1 . 4 ) Importin beta 1 , Ran , and p10 / NTF2 are sufficient to mediate import of activated Smad 3 . ^^^ The import mechanism of Smad 3 shows distinct features from that of the related Smad 2 and the structural basis for this difference maps to the divergent sequences of their N terminal domains . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 , and Smad 4 proteins are important mediators of the antiproliferative responses to TGF beta and may become inactivated in some human cancers . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
IGFBP 3 antiproliferative signalling appears to require an active transforming growth factor beta ( TGF beta ) signalling pathway , and IGFBP 3 stimulates phosphorylation of the TGF beta signalling intermediates Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFbeta stimulation triggers a transient increase in association of Dab 2 with Smad 2 and Smad 3 , which is mediated by a direct interaction between the N terminal phosphotyrosine binding domain of Dab 2 and the MH 2 domain of Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we describe a new role for TGF beta regulated Smad 2 and Smad 3 as components of a ubiquitin ligase complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Two receptor activated Smad proteins , Smad 2 and Smad 3 , are phosphorylated by the activated TGF beta type 1 receptor kinase , after which they partner with the common mediator , Smad 4 , and are translocated to the nucleus to where they participate in transcriptional complexes to control expression of target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta 1 induced modest increases in Smad 2 and Smad 4 mRNA levels without affecting Smad 3 mRNA expression in both cell lines . ^^^ We found that Smad 3 and to a lesser extent , Smad 2 and Smad 4 , enhanced , while Smad 7 inhibited , TGF beta 1 induced transcriptional activities . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The response of HSC to TGFbeta , leading to , e . g . , induction of alpha 2 ( 1 ) collagen expression , is mediated by phosphorylation of Smad 2 and Smad 3 and subsequent nuclear translocation of a Smad containing complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The results showed that Smad 3 and Smad 4 , but not Smad 1 or Smad 2 , mimicked the inhibitory effect of TGF beta and abrogated interleukin 1beta ( IL 1beta ) induced stimulation of MMP 1 promoter activity and NFkappaB specific gene transcription in dermal fibroblasts . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We further used the Smad 7 promoter sequence that contains a Smad binding element ( SBE ) , GTCTAGAC to determine how mutations in each nucleotide in the SBE affects the binding with Smad 5 , compared with the binding with Smad 1 , Smad 2 , Smad 3 , Smad 4 , and Smad 8 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RT PCR analysis revealed that all these cell lines expressed the mRNA of TGF beta 1 , beta 2 , and beta 3 , TGF beta receptors type 1 , 2 , and 3 , and post receptor signaling genes smad 2 , smad 3 , smad 4 , smad 6 , and smad 7 with the exception that TGF beta 2 and smad 3 were undetectable in JAR and JEG 3 cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Furthermore , functional haploinsufficiency of Smad 2 , but not Smad 3 , altered TGF beta mediated tooth development . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We demonstrate that the expression of betaglycan in LLC PK 1 cells results in inhibition of TGF beta signaling as measured by reporter gene expression , thymidine incorporation , collagen production , and phosphorylation of the downstream signaling effectors Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
On TGF beta stimulation , Smad 3 and Smad 2 translocate into the nucleus and induce a rapid degradation of SnoN , allowing activation of TGF beta target genes . ^^^ We show that Smad 2 or Smad 3 induced degradation of SnoN requires the ubiquitin dependent proteasome and can be mediated by the anaphase promoting complex ( APC ) and the UbcH 5 family of ubiquitin conjugating enzymes . ^^^ Smad 3 and to a lesser extent , Smad 2 , interact with both the APC and SnoN , resulting in the recruitment of the APC to SnoN and subsequent ubiquitination of SnoN in a destruction box ( D box ) dependent manner . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Immunoprecipitation and GST pull down assays show that AR directly associates with Smad 3 but not Smad 2 or Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we show that the TGF beta intracellular effector Smad 3 , but not Smad 2 , mediates the inhibition of myogenic differentiation in MyoD expressing C3H10T1 / 2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Overexpression of Smad 3 and 4 , but not of Smad 2 , resulted in a marked down regulation of SeP mRNA expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We show that the DAP kinase promoter is activated by TGF beta through the action of Smad 2 , Smad 3 and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We previously demonstrated in T47D cells transfected to express the transforming growth factor beta receptor type 2 ( TGF betaRII ) that insulin like growth factor binding protein 3 ( IGFBP 3 ) could stimulate Smad 2 and Smad 3 phosphorylation , potentiate TGF beta 1 stimulated Smad phosphorylation , and cooperate with exogenous TGF beta 1 in cell growth inhibition ( Fanayan , S . , Firth , S . ^^^ Like TGF beta 1 , natural and recombinant IGFBP 3 stimulated the time and dose dependent phosphorylation of TGF betaR 1 as well as Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Thus , at a key point in the determination of LR asymmetry , left sided signaling is mediated by the transcription factors Smad 2 and Smad 3 ( regulated by Nodal ) , whereas signaling on the right depends on Smad 1 and Smad 5 ( which are regulated by BMP ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Direct interaction of c Myc with Smad 2 and Smad 3 to inhibit TGF beta mediated induction of the CDK inhibitor p 15 ( Ink4B ) . ^^^ In this study , we reveal that c Myc physically interacts with Smad 2 and Smad 3 , two specific signal transducers involved in TGF beta signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Overexpression of SMAD 2 and SMAD 3 along with SMAD 4 increased transcriptional activity of the mGnRHR gene , which was further increased by GnRH agonist stimulation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Apparently the inhibitory property was specific to Smad 3 as there was no inhibitory effect on the activation of Smad 2 after stimulation with transforming growth factor beta . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 4 protein was undetectable in both cell lines , but Smad 2 and Smad 3 were expressed at levels comparable with a fully TGF beta responsive cell line , and treatment of the cells with TGF beta 1 resulted in the phosphorylation of Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
At day 10 , Smad 6 increased dramatically , Smad 2 , Smad 3 , and Smad 4 remained elevated while Smad 1 and Smad 5 decreased in the fracture callus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
On the basis of its interaction with the DE , we isolated a Xenopus homolog of the human Williams Beuren syndrome critical region 11 ( XWBSCR 11 ) , and further , show that it interacts with pathway specific Smad 2 and Smad 3 in a ligand dependent manner . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Change of gene expression of transforming growth factor beta 1 , Smad 2 and Smad 3 in hypertrophic scars skins ] . ^^^ METHODS : Thirty two cases were detected to compare the gene expression of TGF beta 1 , Smad 2 and Smad 3 with RT PCR . ^^^ RESULTS : TGF beta 1 , Smad 2 and Smad 3 gene expression could all be detected in hypertrophic scars , fetal and adult skins . ^^^ Among 8 groups examinated in this experiment ( each group comprised a hypertrophic scar and its corresponding normal skin ) , there were 5 , 8 and 5 groups in which TGF beta 1 , Smad 2 and Smad 3 gene expression were higher in hypertrophic scars than in normal skins respectively . ^^^ The fetal skins showed significantly lower level of TGF beta 1 and Smad 3 gene expression compared with adult skins ( t = 2 . 204 , P < 0 . 05 and t = 4 . 269 , P < 0 . 01 respectively ) , while mRNA contents of Smad 2 were obviously higher in fetal skins than in adult skins ( t = 6 . 685 , P < 0 . 01 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Absence of Smad 3 had no effect on the ability of TGF beta to inhibit the growth of mammary epithelial cells in culture , and no compensatory changes in expression or activation of Smad 2 were seen in the Smad 3 null epithelium . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Stable transfection of wild type Smad 2 , Smad 3 , or Smad 4 increased TGF beta stimulated PTHrP secretion , whereas dominant negative Smad 2 , Smad 3 , or Smad 4 only partially reduced TGF beta stimulated PTHrP secretion . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The receptor complex recruits and phosphorylates the downstream signaling proteins , Smad 2 and Smad 3 , which then associate with Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Stage specific expression of Smad 2 and Smad 3 during folliculogenesis . ^^^ Smad 2 expression , but not Smad 3 expression , returns in luteal cells . ^^^ Both Smad 2 and Smad 3 are translocated to the nucleus of granulosa cells in response to treatment with either TGFbeta or activin . ^^^ However , Smad 2 is more responsive to activin stimulation , and Smad 3 is more responsive to TGFbeta stimulation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Signal transduction of activin , one of the members in the transforming growth factor beta superfamily , is initiated by ligand binding with two distinct membrane receptors ( type 2 and type 1 ) followed by activation of Smad 2 or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The c Jun N terminal kinase ( JNK ) pathway , another downstream target activated by TGF beta receptors , has also been suggested to inhibit TGF beta signaling through interaction of c Jun with Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signals are mediated by a family of Smad proteins , of which Smad 2 and Smad 3 are downstream intracellular targets of serine / threonine kinase receptors of TGF beta . ^^^ Although Smad 2 and Smad 3 are crucial for TGF beta signaling , little is known about the regulation of their expression . ^^^ In this study , we investigated the expression of Smad 2 and Smad 3 in an in vivo animal model of lung fibrosis induced by bleomycin . ^^^ The decline of Smad 3 mRNA was evident at day three of post bleomycin instillation and the expression of Smad 3 continually decreased during the reparative phase of lung injury ( days 8 and 12 ) , whereas the expression of Smad 2 showed little change after bleomycin administration . ^^^ These studies provide direct evidence for a differential regulation of Smad 3 expression that is distinct from that of Smad 2 during bleomycin induced pulmonary fibrosis and suggest a ligand induced negative feedback loop that modulates cellular TGF beta signaling . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Our data provide evidence that , whereas type 1 receptor phosphorylation and association of SARA and Smad 2 with the TGF beta R complex take place independently of clathrin lattice formation , Smad 2 or Smad 3 activation and downstream signaling only occur after endocytic vesicle formation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are transcription factors that mediate the effects of TGF beta ( 1 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Tax directly interacts with Smad 2 , Smad 3 , and Smad 4 ; the Smad MH 2 domain binds to Tax . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In summary , our analyses point out differences of Smad3b and Smad 2 functions in zebrafish and provide the first link of smad 3 and smad 7 function in context of vertebrate development . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We found that E 7 interacts constitutively with Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Compared with control lungs , Smad mRNA expression was decreased markedly in nitrofen exposed lungs : Smad 2 ( 40 % , P = . 16 ) , Smad 3 ( 29 % , P = . 02 ) , Smad 4 ( 25 % , P = . 07 ) , and Smad 7 ( 36 % , P = . 04 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
SMAD 3 , but not SMAD 2 , mediated the repressor activity of TGF beta on the Sp B promoter . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Two discrete Smad dependent signalling pathways have been identified : TGF beta , Activin and Nodal signal via the Smad 2 ( or Smad 3 ) Smad 4 complex , whereas BMP signals via the Smad 1 Smad4 complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In addition , no significant changes were observed in Smad 2 , Smad 3 , and Smad 4 expression after ultraviolet irradiation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transforming growth factor ( TGF ) beta stimulation leads to phosphorylation and activation of Smad 2 and Smad 3 , which form complexes with Smad 4 that accumulate in the nucleus and regulate transcription of target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
These genes were TGF beta type 1 receptor gene ( TGFBR 1 ) , TGF beta type 2 receptor gene ( TGFBR 2 ) , SMAD 2 gene ( SMAD 2 ) , SMAD 3 gene ( SMAD 3 ) , SMAD 4 gene ( SMAD 4 ) , and SMAD 7 gene ( SMAD 7 ) , all of which compose the TGF beta 1 signaling pathway . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The expression of TGF beta type 2 receptor protein was decreased in two of seven cell lines , and the expression of both Smad 2 and Smad 3 proteins was decreased in only one cell line . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
METHODS : In vivo , TGF beta receptors ( TbetaRs ) , Smad 2 , Smad 3 , and Smad 4 , PAI 1 , and Smad 2 phosphorylation were examined by immunohistochemistry in 3 native aortas , 14 rat aortic syngrafts , and 19 allografts collected at 15 , 30 , and 45 days post transplantation . ^^^ RESULTS : Immunohistochemical staining revealed that vascular parenchymal cells contained TbetaRI , TbetaRII , Smad 2 , Smad 3 , and Smad 4 , known signaling transducers for TGF beta / Smad pathway , in all samples . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
On the other hand , overexpression of Smad 2 and Smad 3 did not elicit any significant increases in CPP32 / caspase 3 activity . ^^^ CONCLUSIONS : These data indicate that TGF beta induced apoptosis in mesangial cells is mediated through the activation of caspase 3 by Smad 7 , but not by Smad 2 or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
They also express TGF beta receptors types 1 and 2 , as well as Smad 2 , Smad 3 , and Smad 4 proteins , which are essential for TGF betabinding and signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We now show evidence that TIEG increases transcription of the Smad 2 gene but not the Smad 3 or Smad 4 genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here , we have constructed recombinant adenoviruses harboring genes for hemagglutinin tagged Smad 2 , Smad 3 , and Smad 4 and used these in dissecting the role of Smads , the signaling mediators of TGF beta , in regulation of endogenous MMP 13 gene expression in human gingival fibroblasts . ^^^ Adenoviral expression of Smad 3 , but not Smad 2 , augmented the TGF beta elicited induction of MMP 13 expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The Hex BRE binds Smad 4 and Smad 1 Smad4 complexes in vitro , and in transfection assays , it is responsive to Smad 1 and Smad 4 but not to Smad 2 and Smad 4 or Smad 3 and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The type 1 receptor phosphorylates and activates the receptor regulated Smads ( R Smads ) , Smad 2 and Smad 3 , which form hetero oligomeric complexes with the co Smad , Smad 4 , and translocate to the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta dependent differentiation of these cells to monocytes , but not retinoic acid dependent differentiation to granulocytes , was accompanied by rapid phosphorylation and nuclear translocation of Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Although Smad 7 expression inhibited both Smad 2 and Smad 3 mediated TGF beta signaling in podocytes , it inhibited only Smad 3 but not Smad 2 signaling in mesangial cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad 2 and Smad 3 proteins as well as stimulation of transcriptional activities of Smad 3 and the transcription factor hypoxia inducible factor 1alpha and culminated in up regulation of TGF beta 2 gene expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Among receptor regulated Smads , c Ski and SnoN bind more strongly to Smad 2 and Smad 3 than to Smad 1 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signals are primarily transduced to the nucleus through complexes of receptor regulated Smads , Smad 2 and Smad 3 with the common mediator Smad , Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We first showed by immunohistochemistry that molecules involved in TGF beta 1 signal transduction , that is , membrane receptors T beta RI and T beta RII and intracellular proteins SMAD 2 , SMAD 3 , and SMAD 4 , were present in human dental cells in vivo and were all maintained after culture of thick sliced teeth in cells undergoing TGF beta 1 stimulation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Our findings indicate that the TGF beta 1 type 1 receptor ALK 5 is expressed by odontoblasts as well as the signal transduction proteins Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signals by binding to its cell surface serine / threonine kinase receptors , which in turn phosphorylate downstream signal transducers , Smad 2 and Smad 3 . ^^^ Phosphorylated Smad 2 and Smad 3 , together with Smad 4 , enter the nucleus and associate with various transcription factors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transfection with Smad 2 but not Smad 3 resulted in TGF beta 1 independent alteration in fibroblast cell phenotype , up regulation of alphaSMA mRNA and reorganization of the actin cytoskeleton . ^^^ Overexpression of the Smad 2 , Smad 3 , or Smad 4 proteins was associated with increased production of all collagen types . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta mediates activation of Smad 2 primarily in early cultured cells and that of Smad 3 primarily in transdifferentiated cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Both molecules are known to present Smad 2 and Smad 3 to the TGF beta receptor complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transfection of Smad 3 , but not the highly related Smad 2 , led to a ligand independent stimulation of the FSHbeta promoter activity . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To investigate the importance of Smad 2 or Smad 3 in this augmentation process , embryo derived fibroblasts from mice lacking expression of Smad 2 or Smad 3 genes were cast into native type 1 collagen gels . ^^^ All three isoforms of TGF beta significantly augmented contraction of collagen gels mediated by fibroblasts with genotypes of Smad 2 knockout ( S2KO ) , Smad 2 wildtype ( S2WT ) , and Smad 3 wildtype ( S3WT ) , but not Smad 3 knockout ( S3KO ) mice . ^^^ These results suggest that expression of Smad 3 but not Smad 2 may be critical in TGF beta augmentation of fibroblast mediated collagen gel contraction . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In addition , overexpression of Smad 2 or Smad 3 , major signal transducing Smads , was sufficient to inhibite the IFN gamma and TNF alpha induced TARC production in HaCaT cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta induced nuclear localization of Smad 2 and Smad 3 in Smad 4 null cancer cell lines . ^^^ The activated transforming growth factor beta ( TGF beta ) receptor phosphorylates Smad 2 and Smad 3 , which then complex with Smad 4 and translocate to the nucleus . ^^^ To study the role of Smad 4 in TGF beta induced translocation of the receptor activated Smads to the nucleus , we analysed by immunofluorescence the cellular localization of endogenous Smad 2 and Smad 3 after TGF beta treatment of VACO 9M , plus four additional Smad 4 null cell lines of breast ( MDA MB 468 ) , or pancreatic ( BxPC 3 , Hs766T , CFPAC 1 ) origin . ^^^ In each cell line , TGF beta treatment resulted in both Smad 2 and Smad 3 moving to the nucleus in a Smad 4 independent fashion . ^^^ Nuclear translocation of Smad 2 and Smad 3 was , however , not sufficient to activate reporters for TGF beta induced transcriptional responses , which were however restored by transient transfection of wild type Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In the present study , we show that Smad 3 and Smad 4 but not Smad 2 physically interact with HNF 4 via their Mad homology 1 domains both in vitro and in vivo . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Developmental and stage specific expression of Smad 2 and Smad 3 in rat testis . ^^^ Smad 2 and Smad 3 are associated with both TGFbeta and activin signaling . ^^^ In the present study , we have determined that Smad 2 and Smad 3 proteins are expressed in the postnatal testes of rats from 5 days to 60 days of age . ^^^ Smad 2 and Smad 3 messenger RNA levels parallel protein expression . ^^^ Smad 2 and Smad 3 proteins are mainly localized in the cytoplasm of meiotic germ cells , Sertoli cells , and Leydig cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
They prolong the activation of Smad 2 induced by TGF beta and markedly enhance the ability of Smad 3 to activate a Smad binding element , CAGA luciferase . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Ac SDKP suppressed not only TGF beta 1 induced Smad 2 phosphorylation at Ser 465 / 467 in a dose dependent manner , but also the nuclear accumulation of receptor regulated Smads ( R Smad ) , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activin a signaling induces Smad 2 , but not Smad 3 , requiring protein kinase a activity in granulosa cells from the avian ovary . ^^^ Interestingly , the effect is specific for Smad 2 , since expression of the structurally and functionally closely related Smad 3 remains entirely unaffected . ^^^ Hence , activin A induces Smad 2 , but not Smad 3 , to high levels requiring PKA activation . ^^^ Since Smad 2 and Smad 3 target distinct yet overlapping sets of TGF beta / activin responsive genes , the selective Smad 2 induction by FSH / activin A could allow FSH to efficiently modulate the transcriptional readout of activin A signaling in avian granulosa cells . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Evidence for a role of Smad 3 and Smad 2 in stabilization of the tumor derived mutant Smad2 . ^^^ Q407R was reversed when this mutant undergoes homo oligomerization with wild type Smad 2 or hetero oligomerization with Smad 3 within the cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signaling involves TGF beta type 1 receptor mediated phosphorylation of serine residues within the conserved SSXS motif at the C terminus of Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Decreased Type 2 receptor expression was accompanied by failure of ulcer fibroblasts to phosphorylate Smad 2 , Smad 3 , and p42 / 44 mitogen activating protein kinase ( MAPK ) , and was associated with a slower proliferative rate in response to TGF beta 1 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The phosphorylation of Smad 2 and Smad 3 by the transforming growth factor ( TGF ) beta activated receptor kinases and their subsequent heterodimerization with Smad 4 and translocation to the nucleus form the basis for a model how Smad proteins work to transmit TGF beta signals . ^^^ The transcriptional activity of Smad 2 Smad4 or Smad 3 Smad4 complexes can be limited by the corepressor Ski , which is believed to interact with Smad complexes on TGF beta responsive promoters and represses their ability to activate TGF beta target genes by assembling on DNA a repressor complex containing histone deacetylase . ^^^ Here we show that Ski can block TGF beta signaling by interfering with the phosphorylation of Smad 2 and Smad 3 by the activated TGF beta type 1 receptor . ^^^ Furthermore , we demonstrate that overexpression of Ski induces the assembly of Smad 2 Smad4 and Smad 3 Smad4 complexes independent of TGF beta signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RESULTS : Activation of Smad signaling , as evidenced by Smad 2 and Smad 3 nuclear translocation and phosphorylation , was found in renal and vascular cells at 24 hours after high glucose stimulation ( up to 55 % increased ) . ^^^ Importantly , overexpression of Smad 7 resulted in marked inhibition of high glucose induced Smad 2 and Smad 3 activation and type 1 collagen synthesis , suggesting that Smad signaling is a key pathway in high glucose mediated renal and vascular scarring . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The total amount of Smad 2 protein remained unchanged before and after TGF beta ( 1 ) treatment , but the expression level of Smad 3 decreased markedly after 24 h treatment and kept dropping by 48 h . ^^^ CONCLUSIONS : The results suggest that the Smad 2 / 3 may be the downstream signal transducers of TGF beta ( 1 ) in human dental pulp cells and Smad 2 / 3 may mediate TGF beta ( 1 ) signaling by translocation early in TGF beta ( 1 ) treatment , while down regulation of Smad 3 expression by TGF beta ( 1 ) at later stage is involved in negative modulation of TGF beta ( 1 ) signaling . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In rat SMC , Smad 1 , Smad 2 , Smad 3 , Smad 4 and Smad 5 were detected by immunoprecipitation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Compared with normal rats , Smad 7 expression within the UUO kidney was significantly reduced , and this was associated with up to a sixfold increase in Smad 2 and Smad 3 activation and severe tubulointerstitial fibrosis . ^^^ In contrast , treatment with inducible Smad 7 resulted in a fivefold increase in Smad 7 expression with complete inhibition of Smad 2 and Smad 3 activation and tubulointerstitial fibrosis in terms of tubulointerstitial myofibroblast accumulation ( 85 % downward arrow ) and collagen 1 and 3 mRNA and protein expression ( 60 to 70 % downward arrow ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We have previously reported that Ski and SnoN interact directly with Smad 2 , Smad 3 , and Smad 4 and repress their ability to activate TGF beta target genes through multiple mechanisms . ^^^ Here , we show that the receptor regulated Smad proteins ( Smad 2 and Smad 3 ) and common mediator Smad ( Smad 4 ) bind to different regions in Ski and SnoN . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Importantly , Smad 3 , but not Smad 2 , was detected in epithelial cell nuclei during all time points examined , indicating that activin signaling is mediated by Smad 3 at these times . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The SKI and SnoN protein family associate with and repress the activity of Smad 2 , Smad 3 , and Smad 4 , three members of the TGF fl signaling pathway . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
YY 1 interacts with the conserved N terminal Mad homology 1 domain of Smad 4 and to a lesser extent with Smad 1 , Smad 2 , and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We recently identified a novel molecule , TLP for TRAP 1 like protein , which selectively interferes with Smad 3 signaling , and are currently investigating whether levels of this protein might be altered in disease to change the relative flow of information from Smad 2 and Smad3 . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
SMAD 2 and SMAD 3 were both present in the MEE , whereas SMAD 2 was the only one phosphorylated during palatal fusion . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Our study , along with recent studies of the nucleocytoplasmic shuttling of Smad 2 and Smad 3 proteins , demonstrate that continued nucleocytoplasmic shuttling is a common requisite for the active signaling of R Smads . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we show that senescence of 5 ras ( Ha ) transduced Smad 3 null keratinocytes is delayed , whereas overexpression of Smad 3 , but not Smad 2 or Smad 4 , induced senescence . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Finally , we show that removal of one copy of Smad 3 in the context of a Smad 2 deficient epiblast results in a failure to specify all axial midline tissues . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Mutational analysis of TGF beta type 2 receptor , Smad 2 , Smad 3 , Smad 4 , Smad 6 and Smad 7 genes in colorectal cancer . ^^^ Then , all coding regions of the TGF beta type 2 receptor ( TRII ) and the genes for Smad 2 , Smad 3 , Smad 4 , Smad 6 , and Smad 7 were analyzed by PCR SSCP and direct sequencing . ^^^ No abnormalities were found in the genes for Smad 2 , Smad 3 , Smad 6 , and Smad 7 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Consistent with an inhibitory role in the BMP signaling pathway , the elevated Smurf 1 markedly reduces the level of endogenous Smad 5 , whereas it leaves unaltered that of Smad 2 , Smad 3 , and Smad 7 , which are components of the TGF beta pathway . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Insulin like growth factor 1 inhibits transcriptional responses of transforming growth factor beta by phosphatidylinositol 3 kinase / Akt dependent suppression of the activation of Smad 3 but not Smad 2 . ^^^ However , Western blot analysis reveals that IGF 1 selectively inhibits the TGF beta triggered activation Smad 3 but not Smad 2 , while not altering expression of total Smads 2 , 3 , or 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Immunoblot analyses of nuclear extracts of embryonic maxillary mesenchymal cells revealed that TGFbeta induced nuclear translocation of Smad 2 and Smad 3 proteins was not affected by EGF . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The aim of our study was to examine expression of Smad proteins i . e . , Smad 2 , Smad 3 and Smad 4 both as mRNA and protein as well as their intracellular localization in normal ( n=13 ) and neoplastic ( n=42 ) endometrial tissue specimens using RT PCR and immunological techniques i . e . , Western blot and ELISA . ^^^ Smad 2 and Smad 3 mRNAs were detected both in uterine carcinosarcoma and rhabdomyosarcoma of the uterine cervix . ^^^ In endometrial cancer as compared to normal endometrium significantly higher levels of Smad 2 and Smad 3 proteins , both in cytoplasmic ( p=0 . 002 ; p=0 . 0001 ) and nuclear ( p=0 . 016 ; p=0 . 0004 ) fractions were observed . ^^^ Both in uterine carcinosarcoma and rhabdomyosarcoma of the uterine cervix Smad 2 , Smad 3 and Smad 4 proteins were not detected . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The proteins examined include activin subunits ( betaA and betaB ) , activin binding protein ( follistatin ) , activin type 2 receptors ( type IIA and IIB ) , the type 1 activin receptor like kinases ( ALK 1 like , ALK 2 like , and ALK 4 like ) , and the intracellular activin signaling molecules ( Smad 2 , Smad 3 , Smad 4 , and Smad 7 ) . ^^^ The results showed that the entire activin signaling system is expressed by the full grown immature zebrafish oocytes ( approximately 0 . 65 mm in diameter ) , including ALK 4 like ( ActRIB ) , ALK 2 like ( ActRIA ) , ActRIIA , ActRIIB , Smad 2 , Smad 3 , Smad 4 , and Smad 7 , therefore supporting our hypothesis that the oocytes are one of the direct targets of activin actions in the zebrafish ovary . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Although Smad 2 , Smad 3 , and extracellular signal regulated kinase ( ERK ) mitogen activated protein kinases ( MAPKs ) have been proposed as key mediators in TGF beta signaling , their functional specificities and interactivity in controlling transcriptional programs in different cell types and ( patho ) physiological contexts are not known . ^^^ We investigated expression profiles of genes controlled by TGF beta in fibroblasts with ablations of Smad 2 , Smad 3 , and ERK MAPK . ^^^ These results suggest a previously uncharacterized hierarchical model of gene regulation by TGF beta in which TGF beta causes direct activation by Smad 3 of cascades of regulators of transcription and signaling that are transmodulated by Smad 2 and / or ERK . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFbeta induces the phosphorylation of Smad 2 and Smad 3 which associate with Smad 4 and translocate to the nucleus where they regulate gene transcription ; besides these stimulatory Smads , the inhibitory Smads , Smad 6 and Smad 7 , oppose signaling by blocking receptors and interrupting the phosphorylation of Smads2 / 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
At the molecular level , this effect is associated with an increase in Smad 1 , Smad 2 and Smad 3 phosphorylation and an increase in alpha 6 and beta 1 integrin expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Upon activation , the TGF beta type 1 receptor phosphorylates Smad 2 and Smad 3 , which then form complexes with Smad 4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate , such as cell cycle components , differentiation factors and cell adhesion molecules . ^^^ Although Smad 2 and Smad 3 are highly homologous and share some overlapping activities , they have distinct functions and are regulated differentially . ^^^ This review is primarily focused on our understanding of the similar as well as distinct function and regulation of Smad 2 and Smad 3 in TGF beta signaling , their physiological roles revealed by knockout studies and their tumor suppressive functions . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Importantly , GPI mutant cells displayed enhanced gene transcriptional activity and Smad 2 and Smad 3 activation in response to TGF beta 1 treatment in a dose dependent manner . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We found that Smad 2 protein decreased markedly in nephritic glomeruli , whereas no significant changes were observed in the levels of Smad 3 and Smad 4 proteins . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In quiescent HSCs , TGF beta signaling involves TGF beta type 1 receptor ( TbetaRI ) mediated phosphorylation of serine residues within the conserved SSXS motif at the C terminus of Smad 2 and Smad 3 . ^^^ The middle linker regions of Smad 2 and Smad 3 also are phosphorylated by mitogen activated protein kinase ( MAPK ) . ^^^ TGF beta activated the p 38 MAPK pathway , further leading to Smad 3 phosphorylation at the linker region in the cultured MFBs , irrespective of Smad 2 . ^^^ Once combined with TbetaRI phosphorylated Smad 2 , the Smad 3 and Smad 4 complex bound to plasminogen activator inhibitor type 1 promoter could enhance the transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We show that Gadd45b is an immediateearly response gene for TGF beta and that the proximal Gadd45b promoter is activated by TGF beta through the action of Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TLP , a novel modulator of TGF beta signaling , has opposite effects on Smad 2 and Smad 3 dependent signaling . ^^^ Consistent with this , TLP inhibits the formation of Smad3 / 4 complexes in the absence of effects on phosphorylation of Smad 3 , while it affects neither Smad 2 phosphorylation nor hetero oligomerization . ^^^ We propose that TLP might regulate the balance of Smad 2 and Smad 3 signaling by localizing Smad 4 intracellularly , thus contributing to cellular specificity of TGF beta transcriptional responses in both normal and pathophysiology . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Differential regulation of TGF beta signaling through Smad 2 , Smad 3 and Smad 4 . ^^^ Smad 2 , Smad 3 and Smad 4 expression were selectively inhibited in differentiation competent cells by using improved antisense molecules . ^^^ By gene expression profiling , we identified TGF beta dependent genes that are differentially regulated by Smad 2 and Smad 3 under regular growth conditions on a genome wide scale . ^^^ We show that Smad 2 , Smad 3 and Smad 4 contribute to the regulation of TGF beta responses to varying extents , and demonstrate , in addition , that these Smads exhibit distinct roles in different cell types . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
By co transfection studies we show that Smad 4 is essential for Muc5ac promoter activation and that it does not synergize with Smad 2 or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
SKI is known to curtail the growth inhibitory activity of tumor growth factor beta through the formation of repressive transcriptional complexes with Smad 2 and Smad 3 at the p 21 ( Waf 1 ) promoter . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Western blot analyses demonstrated that the 59 kDa Smad 2 , 54 kDa Smad 3 , and 64 kDa Smad 4 proteins were expressed in fetal ovaries of untreated baboons at both mid and late gestation and that the level of expression was not significantly altered in late gestation by in vivo treatment with CGS 20267 or CGS 20267 and estrogen . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
When GCTM 1 was cotransfected with AS oligonucleotide of Smad 2 and Smad 3 , the TGF beta induced invasion of GCTM 1 disappeared . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Cell type specific activation of PAK 2 by transforming growth factor beta independent of Smad 2 and Smad 3 . ^^^ PAK 2 activation occurs in fibroblast but not epithelial cell cultures and is independent of Smad 2 and / or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Inhibition of TGFbeta signaling is dose dependent and results in reduced Smad 2 and Smad 3 phosphorylation , nuclear translocation , and up regulation of the TGFbeta target gene Smad 7 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In Smad 4 null HTB 134 cells , DACH 1 inhibited the activation of SBE 4 reporter activity induced by Smad 2 or Smad 3 only in the presence of Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smads could be divided into receptor regulated Smads ( R Smads : Smad 1 , Smad 2 , Smad 3 , Smad 5 , Smad 8 and Smad 9 ) , common mediator Smad ( co Smad : Smad 4 ) , and inhibitory Smads ( 1 Smads : Smad 6 and Smad 7 ) . ^^^ CBFA 1 could interact with Smad 1 , Smad 2 , Smad 3 , and Smad 5 , so it was involved in TGF beta and BMP 2 signal transduction , and played an important role in the bone formation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Using three different experimental approaches , we found that SMAD 3 and SMAD 4 , but not SMAD 2 , mediate transcription from this enhancer . ^^^ Second , silencing of SMAD protein levels using short interfering RNAs revealed that TGFbeta induced activation of the endogenous gadd45beta gene required SMAD 3 and SMAD 4 but not SMAD 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A number of these cell lines carry inactivating mutations of the TGF beta type 2 ( TbetaR 2 ) receptor , and fail to phosphorylate receptor associated Smads , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Interestingly , Smad 3 , not Smad 2 , is the primary mediator for TGF beta 1 induced transactivation of the SM 22 promoter , while Smad 6 and Smad 7 repress such a transactivation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Cortical expression levels of TGF beta 1 , TGF beta 2 , TbetaRII , and Smad 2 , but not TGF beta 3 , Smad 3 , and Smad 4 were increased . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In addition , treatment with GDF 9 induced the phosphorylation of Smad 2 and Smad 3 in P 19 cells , and the stimulatory effect of GDF 9 on the CAGA luciferase reporter was blocked by the inhibitory Smad 7 , but not Smad 6 . ^^^ In conclusion , although GDF 9 binds to the BMP activated type 2 receptor , its downstream actions are mediated by the type 1 receptor , ALK 5 , and the Smad 2 and Smad 3 proteins . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Distinct roles of Smad 2 , Smad 3 , and ERK dependent pathways in transforming growth factor beta 1 regulation of pancreatic stellate cellular functions . ^^^ Immunoprecipitation and immunocytochemistry revealed that Smad 2 , Smad 3 , and Smad 4 were functionally expressed in PSCs . ^^^ Adenovirus mediated expression of Smad 2 , Smad 3 , or dominant negative Smad2 / 3 did not alter TGF beta ( 1 ) mRNA expression level or the amount of autocrine TGF beta ( 1 ) peptide . ^^^ We propose that TGF beta ( 1 ) differentially regulates PSC activation , proliferation , and TGF beta ( 1 ) mRNA expression through Smad 2 , Smad 3 , and ERK dependent pathways , respectively . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Interaction with Smad 4 is indispensable for suppression of BMP signaling by c Ski . c Ski is a transcriptional corepressor that interacts strongly with Smad 2 , Smad 3 , and Smad 4 but only weakly with Smad 1 and Smad 5 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Both SMAD 2 and SMAD 3 mediate activin stimulated expression of the follicle stimulating hormone beta subunit in mouse gonadotrope cells . ^^^ Because SMAD 7 functions by preventing access of SMAD 2 and SMAD 3 to ALK 4 , these data suggested that both activins and ALK 4 require SMAD 2 and / or SMAD 3 to affect FSHbeta transcription . ^^^ Consistent with this idea , activin A stimulated SMAD 2 and SMAD 3 phosphorylation and nuclear translocation within 5 10 min in LbetaT 2 cells . ^^^ To assess more directly roles for both SMAD 2 and SMAD 3 in activin stimulated FSHbeta expression , RNA interference was used to decrease endogenous SMAD protein levels in LbetaT 2 cells . ^^^ Activin A and ALK4T206D stimulated transcription of the FSHbeta gene were significantly attenuated by the depletion of either SMAD 2 or SMAD 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad7 / v ras ( Ha ) tumors had elevated proliferation and defective nuclear localizaton of Smad 2 , Smad 3 , and Smad 5 , whereas only Smad 5 was altered in Smad6 / v ras ( Ha ) tumors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Although the point mutated Smad4s are expressed at normal levels in these colorectal cancer cells , they can not interact with either TGF beta induced phosphorylated Smad 2 or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad3D407E was not phosphorylated by the constitutively active form of the TGF beta type 1 receptor , and inhibited the phosphorylation of co expressed wild type Smad 2 and Smad 3 . ^^^ Smad2D450E suppressed the phosphorylation of Smad 2 , but did not affect the phosphorylation of Smad 3 , while Smad3D407E blocked the phosphorylation of both Smad 2 and Smad 3 . ^^^ Consistent with these results , Smad2D450E reduced hetero oligomer formation of Smad 2 with Smad 4 , but not of Smad 3 with Smad 4 , while Smad3D407E reduced hetero oligomer formation of both Smad 2 and Smad 3 with Smad 4 . ^^^ However , Smad2D450E reduced the binding of Smad 3 to a target DNA element as well as Smad 2 binding , and Smad2D450E had inhibitory effects on the transcriptional activity of several targets , as Smad3D407E did . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We report results of an association study between BMD and nine candidate genes ( TGFB 1 , TGFBR 2 , SMAD 2 , SMAD 3 , SMAD 4 , IFNB 1 , IFNAR 1 , FOS and LRP 5 ) , as well as of a case control study of osteoporosis . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Coimmunoprecipitation studies indicated that Smad 7 and Smad 2 , but not Smad 3 or 4 , interact with AMSH 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are intracellular signal transduction proteins of importance in transforming growth factor beta ( TGFbeta ) mediated inhibition of epithelial cell proliferation . ^^^ Inactivating mutations in the Smad 2 and Smad 3 genes have been found in various human malignancies . ^^^ In histological appearance , the Matrigel plugs with Smad 2 transfected cells showed strongly reduced cell density , proliferation and angiogenesis compared with the small tumour nodules of similar size formed by the vector or Smad 3 transfected cells . ^^^ Overexpression of Smad 2 and Smad 3 in Mv1Lu cells led to the inhibition of cell growth in three dimensional cultures when compared with vector transfected cells . ^^^ Overexpression of Smad 2 and Smad 3 also decreased the hyperphosphorylation of pRb in Smad transfected cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
METHODS : Lipofectin method was used to transfect Smad 2 , Smad 3 and Smad 7 vectors into MsC ; and immunofluorescence , RT PCR and Western blot analysis were used to detect their transfection efficiency . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In parallel , the signaling of TGF beta 1 reflected by the relative phosphorylation and nuclear translocation of Smad 2 and Smad 3 was reduced in the obstructed kidney of CD 44 ( / ) mice . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We demonstrate that this compound selectively and concentration dependently inhibits ALK 4 , ALK 5 , and ALK 7 dependent activation of downstream cytoplasmic signal transducers , Smad 2 and Smad 3 , and of TGF beta induced mitogen activated protein kinase pathway components but does not alter ALK 1 , ALK 2 , ALK 3 or ALK 6 induced Smad signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
F box protein beta TrCP 1 in this E 3 ligase interacts with Smad 4 both in yeast and in mammalian cells , but has no interaction with Smad 2 and has weak interaction with Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Examination of the signaling pathways involved revealed that TGF beta activation of Smad 2 and Smad 3 appear to be essential for the observed differentiation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We also demonstrate that the amino terminal region of tuberin interacts specifically with the MH 2 domain of SMAD 2 and SMAD 3 proteins to regulate TGF beta 1 responsive genes such as p 21 ( CIP ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate gene expression of transforming growth factor beta ( 1 ) ( TGF beta ( 1 ) ) and its two upstream signalling factors ( smad 2 and smad 3 ) in fetal skin at different gestational ages and postnatal skin and its potential biological significance . ^^^ After morphological characteristics of skin at different developmental stages were examined histologically , gene expressions of TGF beta ( 1 ) , smad 2 and smad 3 in skin specimens at different developmental stages were examined with reverse transcription polymerase chain reaction analysis ( RT PCR ) . ^^^ RESULTS : Gene expression of TGF beta ( 1 ) , smad 2 and smad 3 could all be detected in fetal skin and skin after birth . ^^^ The relative lack in expression of TGF beta ( 1 ) and smad 2 genes in skins from younger fetuses might contribute to fetal scar less healing , in which the role of smad 3 needs to be further investigated . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Sensitivity to TGF beta 1 was also determined by [ 3H ] thymidine incorporation , flow cytometry , phosphorylation of Smad 2 , and total levels of Smad 2 and Smad 3 in these cell lines and in six additional cancer cell lines . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Combinatorial activities of Smad 2 and Smad 3 regulate mesoderm formation and patterning in the mouse embryo . ^^^ TGFbeta / activin / Nodal receptors activate both Smad 2 and Smad 3 intracellular effector proteins . ^^^ Thus , loss of Smad 3 in the context of one wild type copy of Smad 2 results in impaired production of anterior axial mesendoderm , while selective removal of both Smad 2 and Smad 3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives . ^^^ Finally , we demonstrate that Smad 2 ; Smad 3 double homozygous mutants entirely lack mesoderm and fail to gastrulate . ^^^ Collectively , these results demonstrate that dose dependent Smad 2 and Smad 3 signals cooperatively mediate cell fate decisions in the early mouse embryo . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activated by type 2 receptors , the type 1 receptor phosphorylates , thereby activating its effectors Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
After stimulation by TGF beta , Smad 2 and Smad 3 become phosphorylated by the activated TGF beta receptor kinases , oligomerize with Smad 4 , translocate to the nucleus and regulate the expression of TGF beta target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
DNA affinity precipitation analysis revealed that c Ski enhances the binding of Smad 2 and 4 , and to a lesser extent Smad 3 , to both CAGA and TGF beta 1 inhibitory element probes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Biochemical studies in mammalian cells demonstrated that Smad 5 binds to both known mammalian isoforms of Suv39h proteins , and that Smad proteins activated by the TGF beta signaling pathway , Smad 2 and Smad 3 , do not bind with significant affinity . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The roles of Smad 2 and Smad 3 in the development of chemically induced skin tumors in mice . ^^^ To determine the effect of disrupting Smad genes and TGF beta signaling on chemically induced skin carcinogenesis in mice , transgenic mice heterozygous for Smad 2 or Smad 3 deletions and wild type controls were treated with topical dimethylbenzanthracene for 7 months . ^^^ There was a significant difference ( P < 0 . 05 ) in tumor type between Smad 2 ( + / ) and Smad 3 ( + / ) groups , suggesting that Smad 2 and Smad 3 may regulate different targets . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 , and Smad 4 proteins are signaling molecules by which TGF beta modulates gene transcription . ^^^ METHODS AND RESULTS : Immunohistochemistry and reverse transcription polymerase chain reaction demonstrated Smad 2 , Smad 3 , and Smad 4 expression in macrophages of fibrofatty lesions and their upregulation after differentiation of monocytes to macrophages . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Three families of Smad proteins have been identified : receptor regulated Smad 2 and Smad 3 , common partner Smad 4 , and inhibitory Smad 7 ( part of a negative feedback loop ) . ^^^ Compared with sham operated kidneys , the level of Smad 7 protein , but not mRNA , decreased progressively in UUO kidneys , whereas immunoreactivity for nuclear phosphorylated Smad 2 and Smad 3 and renal fibrosis were inversely increased . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 coordinately regulate craniofacial and endodermal development . ^^^ TGF beta , activins , and nodal ligands operate through the highly homologous Smad 2 and Smad 3 intracellular mediators . ^^^ Smad 2 mutants exhibit early embryonic lethality , while Smad 3 mutants are viable , but show a plethora of postnatal phenotypes , including immune dysfunction and skeletal abnormalities . ^^^ Previously , we have shown that the Smad 2 and Smad 3 genes function cooperatively during liver morphogenesis . ^^^ Here we show that Smad 2 and Smad 3 are required at a full dosage for normal embryonic development . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Myostatin signaling through Smad 2 , Smad 3 and Smad 4 is regulated by the inhibitory Smad 7 by a negative feedback mechanism . ^^^ We have also shown that Smad 7 expression is stimulated by myostatin via the interaction between Smad 2 , Smad 3 , Smad 4 and the SBE ( Smad binding element ) in the Smad 7 promoter . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
They include Smad 2 and Smad 3 , which are recognized by TGF beta and activin receptors , and Smads 1 , 5 , 8 , and 9 , which are recognized by bone morphogenetic protein ( BMP ) receptors . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Gly BSA treated cells enhanced Smad 2 and Smad 3 protein levels 2 . 5 times the control levels in the nuclei . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFbeta binds to and activates serine / threonine kinase receptors that phosphorylate Smad 2 and Smad 3 intracellular signal transducers at two C terminal serine residues . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Our present data based on selective interference with activation of endogenous Smad 2 and Smad 3 by stable expression of a mutant form of the TGF beta type 1 receptor ( RImL 45 ) unable to bind Smad2 / 3 but with a functional kinase again show that reduction in Smad2 / 3 signaling by expression of RImL 45 enhanced the malignancy of xenografted tumors of the well differentiated MCF10A derived tumor cell line MCF10CA1h , resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We have described previously the use of microarray technology to identify novel target genes of TGF beta ( transforming growth factor beta ) signalling in mouse embryo fibroblasts deficient in Smad 2 or Smad 3 [ Yang , Piek , Zavadil , Liang , Xie , Heyer , Pavlidis , Kucherlapati , Roberts and Bttinger ( 2003 ) Proc . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The levels of Smad 2 and Smad 3 phosphorylation upon TGF beta 1 or alpha2beta1 integrin ( Type 2 collagen ) stimulation were analyzed by Western blotting techniques . ^^^ Combined stimulation led to a synergistic increase in the phosphorylation of Smad 2 and Smad 3 . ^^^ Type 2 collagen modulates the TGF signaling cascade involving Smad 2 and Smad 3 leading to an increase in Type 2 collagen transcription . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We report the following findings : first , TGF beta is capable of inducing the transcriptional activity of a reporter gene construct corresponding to the +54 / +74 region of the APP promoter , named APP ( TRE ) ( APP TGF beta responsive element ) ; secondly , although this effect is mediated by a transduction pathway involving Smad 3 ( signalling mother against decapentaplegic peptide 3 ) and Smad 4 , Smad 2 or other Smads failed to induce the activity of APP ( TRE ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transforming growth factor beta ( TGF beta ) signalling leads to phosphorylation and activation of receptor regulated Smad 2 and Smad 3 , which form complexes with Smad 4 and accumulate in the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Of interest , the results of small interfering ( si ) RNA experiments provided evidence for differential TGF beta Smad signaling for an early vs . late SMC marker gene in that SMalphaA promoter activity was dependent on both Smad 2 and Smad 3 whereas SMMHC activity was Smad 2 dependent . ^^^ These results are the first to provide direct evidence that TGF beta 1 signaling through Smad 2 and Smad 3 plays an important role in the development of SMCs from totipotential ESCs . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
While SMAD 2 was not expressed and SMAD 3 and 4 displayed no change , the inhibitory SMAD 6 and 7 were significantly down regulated in COPD . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
RESULTS : MDPC 23 cells expressed Smad 2 , Smad 3 and Smad 4 mRNA . ^^^ Endogenous Smad 2 , Smad 3 and Smad 4 rapidly translocated from the cytoplasm into the nucleus in response to TGF beta 1 . ^^^ In contrast to Smad 3 , wild type Smad 2 or its dominant negative mutant had little effect on TGF beta 1 regulation of the promoter activity of DSPP . ^^^ CONCLUSIONS : Smad 2 , Smad 3 and Smad 4 are present and activated by TGF beta 1 in MDPC 23 cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
These cells also have impaired phosphorylation and nuclear translocation of the TGF beta signalling proteins Smad 2 and Smad 3 , as well as impaired induction of TGF beta target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In the present study , we determined that pulmonary arteries in normal lungs and in lungs of patients with emphysema and idiopathic pulmonary arterial hypertension comparably expressed transforming growth factor beta receptors 1 and 2 , Smad ( 1 , 5 , 8 ) , Smad 2 , Smad 3 , Smad 4 , phosphorylated Smad ( 1 , 5 , 8 ) , and phosphorylated Smad 2 ( the latter two both indicative of active in vivo signaling ) in endothelial cells , as assessed by immunohistochemistry and quantitative morphometry . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Overexpression of SMAD 3 ( mediator of decapentaplegic related protein 3 ) , but not of SMAD 2 , increased transcriptional activation of the rat ( r ) FSHbeta gene promoter , which was further enhanced by the combined overexpression of SMAD 3 and 4 ( 3+4 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The aim of this study was to assess the relationship between the expression of TGF beta cascade components , including TGF beta receptor type 1 ( TGF beta RI ) and type 2 ( TGF beta RII ) , SMAD 2 , SMAD 3 , SMAD 4 , and clinicopathological features tumor grade , FIGO classification , and depth of myometrial invasion of type 1 ( endometrioid type ) ECs to give some insight into the role of TGF beta cascade components in endometrial tumorigenesis . ^^^ METHODS : The expression of TGF beta RI , TGF beta RII , SMAD 2 , SMAD 3 , and SMAD 4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction ( RT PCR ) and ELISA , respectively . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are key signaling molecules downstream of the cell surface receptor of transforming growth factor beta ( TGF beta ) or activin . ^^^ These findings indicate that during healing of corneal epithelial defects , endogenous TGF beta activates p38MAPK for cell migration and suppression of cell proliferation and up regulates Smad 7 for inhibition of Smad 2 and Smad 3 signaling , resulting in rapid initial resurfacing of the epithelium . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Moreover , NEDD 4 2 bound to TGF beta specific R Smads , Smads 2 and 3 , in a ligand dependent manner , and induced degradation of Smad 2 , but not Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Exogenous activin , possibly working through intracellular smad 2 and / or smad 3 , as well as exogenous exendin 4 ( a long acting glucagon like peptide 1 agonist ) have both been shown to induce insulin positive / endocrine differentiation in AR42J cells . ^^^ In particular , insulin positive differentiation seems to entail an exendin 4 induced drop in smad 2 and elevation in smad 3 in RNA levels . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To address these questions , we have utilized a human breast cancer cell line MCF10CA1h and demonstrate that p 38 MAP kinase and Rho / ROCK pathways together with Smad 2 and Smad 3 are necessary for TGF beta mediated growth inhibition of this cell line . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Increased cardiac expression of ACE was paralleled by a reciprocal decrease in cardiac AcSDKP and a proportionate increase in phosphorylated Smad 2 and Smad 3 , all of which normalized after both ACE inhibition and AcSDKP infusion . ^^^ CONCLUSIONS : Our findings suggest that increased cardiac ACE activity can increase cardiac collagen content by degradation of AcSDKP , an inhibitor of the phosphorylation of transforming growth factor beta signaling molecules Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
METHODS : We evaluated the time course of TGF beta 1 fibronectin , Smad 2 and Smad 3 protein expression and Smad 3 activation in glomeruli from spontaneously diabetic Otsuka Long Evans Tokushima Fatty ( OLETF ) rats , using immunohistochemistry and Western blot analysis . ^^^ RESULTS : The glomeruli of diabetic OLETF rats showed not only accelerated activation of Smad 3 , but also enhanced protein expression of Smad 2 and Smad 3 , which occurred in parallel to the increased expression of TGF beta and fibronectin compared with glomeruli of control , Long Evans Tokushima Otsuka ( LETO ) rats at 30 weeks of age . ^^^ No differences were found in TGF beta 1 fibronectin , Smad 2 and Smad 3 protein expression and Smad 3 activation in glomeruli between the two strains at 12 weeks of age when OLETF rats were not diabetic . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
This effect was mimicked by a constitutively active ALK 7 ( ALK 7 ca ) but blocked by dominant negative mutants of ALK 7 , Smad 2 , or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The earliest response occurring within 1 2 h after TGF beta 1 administration was an induction and activation of R Smads ( Smad 2 and Smad 3 ) and Co Smad ( Smad 4 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
However , the expression of Smad 3 was not affected . 2 ) High osmolality as such ( using mannitol ) did not affect the TGF beta 1 Smad signaling pathway . 3 ) Losartan inhibited the expression of Smad 2 on the gene level but not on the protein level . 4 ) HG up regulated the level of TGF beta 1 with increasing dextrose concentration , while losartan partially inhibited this effect of HG on releasing of TGF beta 1 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We have previously shown that Smad 2 and Smad 3 insufficiency leads to a loss of bile ducts . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Quercetin also strongly suppressed the basal expression of Smad 2 , Smad 3 , and Smad 4 as well as the phosphorylation of Smad 2 and Smad 3 and the formation of the Smad 2 Smad3 Smad 4 complex . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signals via membrane bound serine / threonine kinase receptors which transmit their signals via the intracellular signalling molecules Smad 2 , Smad 3 and Smad 4 . ^^^ Smad 2 and Smad 3 act as kinase substrates for the receptors , and , following phosphorylation , they form complexes with Smad 4 and translocate to the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A part of the liver specimens were preserved for pathologic examination and the other part was frozen for the detection of mRNA level of Smad 2 , Smad 3 , Smad 4 and Smad 7 . ^^^ RESULTS : The level of Smad 3 mRNA was significantly higher than that of control at the later stage , while the mRNA level of Smad 2 decreased at 12 and at 24 weeks , respectively . ^^^ CONCLUSION : Smad 3 may induce the development of liver fibrosis in mice infected by S . japonicum while Smad 2 may induce the development of liver fibrosis at early stage and inhibit it at later stage . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
MAN 1 , an integral protein of the inner nuclear membrane , binds Smad 2 and Smad 3 and antagonizes transforming growth factor beta signaling . ^^^ We show that the nucleoplasmic , C terminal domain of human MAN 1 binds to Smad 2 and Smad 3 and antagonizes signaling by transforming growth factor beta ( TGF beta ) . ^^^ In direct two hybrid assays , this portion of MAN 1 bound to Smad 2 and Smad 3 . ^^^ In glutathione S transferase precipitation assays , the C terminal domain of MAN 1 bound to Smad 2 and Smad 3 under stringent conditions . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Our findings indicate that Smad 3 has a stronger potential to stimulate the SOX 9 dependent transcriptional activity by modulating the interaction between SOX 9 and CBP / p300 , rather than Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We examined the effect of TGF beta 1 on VEGF production by fibroblasts from mice lacking expression of Smad 2 or Smad 3 as well as human lung fibroblasts treated with or without Smad 2 or Smad 3 siRNA . ^^^ These result suggest that TGF beta 1 stimulation of VEGF production by fibroblasts is regulated by Smad 3 but not by Smad 2 signaling . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 are closely related effectors of TGFbeta / Nodal / Activin related signaling . ^^^ Smad 3 mutant mice develop normally , whereas Smad 2 plays an essential role in patterning the embryonic axis and specification of definitive endoderm . ^^^ Directed expression of either Smad 2 ( Deltaexon 3 ) or Smad 3 , but not Smad 2 ( FL ) , restores the ability of Smad 2 deficient embryonic stem ( ES ) cells to contribute descendants to the definitive endoderm in wild type host embryos . ^^^ Moreover , introducing a human Smad 3 cDNA into the mouse Smad 2 locus similarly rescues anterior posterior patterning and definitive endoderm formation and results in adult viability . ^^^ Collectively , these results demonstrate that the short Smad 2 ( Deltaexon 3 ) isoform or Smad 3 , but not full length Smad 2 , activates all essential target genes downstream of TGFbeta related ligands , including those regulated by Nodal . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Ectopic Smad 2 or Smad 3 together with Smad 4 enhanced , whereas dominant negative forms of Smad 2 , Smad 3 , or Smad 4 , and wild type inhibitory Smad 7 , blocked TGF beta induced EMT . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In addition , BMP specific Smads , Smad 1 , Smad 5 , and especially Smad 8 , induce endogenous p 21 mRNA and protein levels , while they fail to induce epithelial growth inhibition when compared to TGF beta receptor phosphorylated Smads ( R Smads ) , Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta exerts its biological functions mainly through its downstream signalling molecules , Smad 2 and Smad 3 . ^^^ It is now clear that Smad 3 is critical for TGF beta ' s pro fibrotic effect , whereas the functions of Smad 2 in fibrosis in response to TGF beta still need to be determined . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Cloning of Smad 2 , Smad 3 , Smad 4 , and Smad 7 from the goldfish pituitary and evidence for their involvement in activin regulation of goldfish FSHbeta promoter activity . ^^^ To assess the involvement of intracellular signaling protein Smads in regulating goldfish FSHbeta promoter , we first cloned full length cDNAs for goldfish Smad 2 , Smad 3 , Smad 4 , and Smad 7 from the pituitary . ^^^ In addition , we demonstrated that activin induced Smad 3 and Smad 7 expression , but not Smad 2 and Smad 4 . ^^^ Co transfection of Smad 2 or Smad 3 cDNA into the LbetaT 2 cells with the reporter construct of goldfish FSHbeta promoter significantly enhanced basal and activin stimulated reporter ( SEAP , secreted alkaline phosphatase ) expression , while Smad 7 completely blocked basal and Smad2 / 3 stimulated FSHbeta activity . ^^^ Interestingly , the effect of Smad 3 was much higher than that of Smad 2 , suggesting that Smad 3 is likely the principal signal transducing molecule involved in activin stimulation of FSHbeta expression in the goldfish . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Specifically , beta ( 3 ) integrin deficiency is associated with elevated TGF beta receptor 1 and receptor 2 expression , reduced Smad 3 levels , sustained Smad 2 and Smad 4 nuclear localization and enhanced TGF beta 1 mediated dermal fibroblast migration . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Acceleration of Smad 2 and Smad 3 phosphorylation via c Jun NH ( 2 ) terminal kinase during human colorectal carcinogenesis . ^^^ Using antibodies specific to each phosphorylation site , we herein showed that Smad 2 and Smad 3 were phosphorylated at COOH terminal regions but not at linker regions in normal colorectal epithelial cells and that pSmad2 / 3C were located predominantly in their nuclei . ^^^ However , the linker regions of Smad 2 and Smad 3 were phosphorylated in 31 sporadic colorectal adenocarcinomas . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Activin signals through a pathway that involves the activation of the transcriptional coregulators Smad 2 and Smad 3 . ^^^ Previous work from our laboratory demonstrated that Smad 3 , and not Smad 2 , is sufficient for stimulation of the rat FSH ( beta ) promoter in a pituitary derived cell line L ( beta ) T 2 . ^^^ Here , we used RNA interference technology to independently decrease the expression of Smad proteins in L ( beta ) T 2 cells to further investigate Smad 2 and Smad 3 roles in activin dependent regulation of the FSHbeta promoter . ^^^ Down regulation of Smad 2 protein by small interfering RNA duplexes affects only basal transcription of FSH ( beta ) , whereas decreased expression of Smad 3 abrogates activin mediated stimulation of FSH ( beta ) transcription . ^^^ Although highly related , Smad 2 and Smad 3 differ in their Mad homolog ( MH ) 1 domains , where the Smad 2 protein contains two additional stretches of amino acids that prevent this factor from binding to DNA . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signaling involves phosphorylation of Smad 2 and Smad 3 at linker and C terminal regions . ^^^ Although linker phosphorylated Smad 2 remained in the cytoplasm of alpha smooth muscle actin immunoreactive mesenchymal cells adjacent to necrotic hepatocytes in centrilobular areas , linker phosphorylated Smad 3 accumulated in the nuclei . c Jun N terminal kinase ( JNK ) in the activated HSCs directly phosphorylated Smad2 / 3 at linker regions . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Upon stimulation by the transforming growth factor beta ( TGF beta ) , Smad 2 and Smad 3 are phosphorylated at their C termini and assemble into stable heteromeric complexes with Smad 4 . ^^^ Indeed tumorigenic mutations in Smad 4 that affect its interaction with Smad 2 or Smad 3 impair nuclear accumulation of Smad 4 in response to TGF beta . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta signaling pathway involves activation of Smad 2 and Smad 3 by the type 1 receptor and formation of Smad2 / 3 / 4 heteromeric complexes that enter the nucleus to regulate transcription . ^^^ We found that MC 26 cells expressed Smad 2 , Smad 3 , and Smad 4 mRNAs by reverse transeription polymerase chain reaction and confirmed that the TGF beta signaling pathway is functional using a transient transfection assay with 3TP Lux reporter plasmid . ^^^ When MC 26 cells were transiently transfected with dominant negative carboxyl terminal truncation mutants of Smad 2 , Smad 3 , and Smad 4 , TGF beta induced 3TP Lux reporter activity was significantly reduced , suggesting that Smad 2 , Smad 3 , and Smad 4 are attractive novel therapeutic targets for regulating TGF beta signaling in colorectal cancers . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Recently , it was reported that Smad 2 but not Smad 3 regulates TSP 1 expression in response to TGF beta 1 in rat tubular epithelial cells as well as in mouse fibroblasts . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The constitutively active forms of SMAD 2 and SMAD 3 were both capable of inhibiting endothelial cell proliferation , whereas the dominant negative forms of SMAD 3 and SMAD 4 released the inhibitory effect of activin A on endothelial cell proliferation by only 20 % . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Because Evi 1 interacts with the highly conserved MH 2 domain of Smad 3 , we investigated the physical and functional interaction of Evi 1 with Smad 1 and Smad 2 , downstream targets of BMP and activin signaling , respectively . ^^^ Evi 1 interacted with and repressed the receptor activated transcription through Smad 1 and Smad 2 , similarly to Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Upon TGF beta binding the TGF beta type 1 receptor phosphorylates Smad 2 and Smad 3 , which then complex with Smad 4 and translocate to the nucleus , with subsequent activation of target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Lack of Galphai 2 resulted in decreased phosphorylation of Smad 2 and Smad 3 in T cells at the basal levels as well as at the late but not early phase of TGF beta stimulation , which appears to be ascribed to differential expression of neither cell surface TGF beta receptors nor Smad 7 . ^^^ The altered phosphorylation of Smad proteins involves phospholipase C mediated signaling , a downstream signaling molecule of Galphai 2 , because phospholipase C inhibitors could restore Smad 2 and Smad 3 phosphorylation in Galphai 2 ( / ) T cells at levels comparable to that in wild type T cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Influence of exogenous TGFbeta 1 on the expression of smad 2 and smad 3 in rat bone marrow derived mesenchymal stem cells . ^^^ The expression of Smad 2 and Smad 3 and the influence of exogenous transforming growth factorbeta 1 ( TGFbeta 1 ) on them in rat bone marrow derived mesenchymal stem cells ( MSCs ) cultured in vitro were investigated . ^^^ The expression of Smad 2 and Smad 3 and the influence of exogenous TGFbeta 1 , on them were also examined by immunocytochemistry and Western blot assays . ^^^ Smad 2 and Smad 3 proteins were detected only in the cytoplasm in the absence of TGFbeta 1 , and TGFbeta 1 , could stimulate the translocation of them from the cytoplasm to the nucleus . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In addition to interacting stably with the activated TGF beta type 1 receptor ( TbetaRI ) to prevent phosphorylation of the receptor regulated Smads ( Smad 2 and Smad 3 ) , Smad 7 also induces degradation of the activated TbetaRI through association with different E 3 ubiquitin ligases . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
CTGF enhanced TGFbeta induced phosphorylation and nuclear translocation of Smad 2 and Smad 3 in mesangial cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
These findings were corroborated by studies using siRNAs to Smad 2 and 3 where siRNA to Smad 2 but not to Smad 3 inhibited the TGF beta 1 induction of fibronectin synthesis . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
To further confirm inhibitory effect of genistein in MC 26 cells require TGF beta1 / Smad signaling , we employed Western blot and electrophoretic mobility shift assay to detect formation of Smad DNA complexes and phosphorylation of Smad 2 and Smad 3 , respectively . ^^^ Data revealed that genistein induced an evident formation of Smad DNA complexes and phosphorylation of Smad 2 and Smad 3 , indicating increased TGF beta 1 signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 ( Smad2 / 3 ) proteins are key signaling molecules for TGF beta and some related family members regulating the transcription of several hundred genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 play different roles in rat hepatic stellate cell function and alpha smooth muscle actin organization . ^^^ To characterize the function of the TGF beta signaling intermediates Smad 2 and Smad 3 in HSC , we infected primary rat HSC in culture with adenoviruses expressing wild type and dominant negative Smads 2 and 3 . ^^^ Smad 3 overexpressing cells exhibited increased deposition of fibronectin and type 1 collagen , increased chemotaxis , and decreased proliferation compared with uninfected cells and those infected with Smad 2 or either dominant negative , demonstrating different biological functions for the two Smads . ^^^ Additionally , coinfection experiments suggested that Smad 2 and Smad 3 signal via independent pathways . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Notch4ICD was found to bind to Smad 2 , Smad 3 and Smad 4 but with higher affinity to Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In GST pull down experiments , UCH 37 bound weakly to Smad 2 and Smad 3 , and bound very strongly to Smad 7 in a region that is distinct from the PY motif in Smad 7 that interacts with Smurf ubiquitin ligases . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Combinations of Smad 2 or Smad 3 with Smad 4 stimulate hDio 3 gene transcription only in cells that express endogenous D 3 activity , indicating that Smads are necessary but not sufficient for D 3 induction . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In another set of experiments , wild type ( wt ) , Smad 2 null ( Smad 2 / ) and Smad 3 null ( Smad 3 / ) mouse embryonic fibroblasts ( MEF ) were assayed for cell proliferation and collagen production after serum free co culture with KK or exposure to conditioned media collected from serum free KK / KF co culture . ^^^ Upregulation of TGFbetaR 1 and TGFbetaR 2 , Smad 3 and p Smad 2 was observed in KF co cultured with KK , together with enhanced Smad 3 phosphorylation and Smad2 / 3 / 4 binding complex production . ^^^ When MEF wt , MEF Smad 2 / or MEF Smad 3 / were co cultured with KK or exposed to KK / KF co culture conditioned media , enhanced proliferation and collagen production were seen in MEF wt and MEF Smad 2 / but not in MEF Smad 3 / cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We show that Smad 2 and Smad 3 have different effects on the dynamics of TGFbeta 1 induced protein phosphorylation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 3 , but not Smad 2 , overexpression enhanced the TGFbeta 1 effects . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Dissection of the molecular steps involved in TGF beta signaling revealed that N acetyl L cysteine dose dependently abrogated the induction of the TGF beta 1 signaling reporter gene activation , the phosphorylation of Smad 2 and Smad 3 , and the up regulation of Smad 7 mRNA . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In the nucleus , SnoN binds to Smad 2 , Smad 3 , and Smad 4 and represses their ability to activate transcription of TGF beta target genes through multiple mechanisms . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In this study , we succeeded in simultaneous stable knockdown of transforming growth factor beta ( TGF beta ) pathway related Smads Smad 2 , Smad 3 and Smad 4 at the cellular level . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In response to transforming growth factor beta ( TGF beta ) , Smad 4 forms complexes with activated Smad 2 and Smad 3 , which accumulate in the nucleus , where they both positively and negatively regulate TGF beta target genes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 and Smad 3 were phosphorylated in response to activin and accumulated in the nucleus of treated T47D cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
By using a model of adult rat exposed in utero to 0 , 0 . 4 , 2 , or 10 mg / kg . d flutamide , we observed that pro TGF beta signaling members , such as the three isoforms of TGF beta ligands ( TGF beta 1 3 ) , the two TGF beta receptors ( TGF betaRI and RII ) and the R Smads Smad 1 , Smad 2 , Smad 3 , and Smad 5 were inhibited at the mRNA and protein levels , whereas the anti TGF beta signaling member Smad 7 was overexpressed . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Stable cell clones expressing Smad 2 or Smad 3 dominant negative mutants , or wild type Smad 7 were constructed to investigate the role of Smad proteins in the mediation of apoptosis by TGF beta 1 in MDPC 23 cells . ^^^ Transfection of dominant negative mutant forms of Smad 2 or Smad 3 blocked TGF beta 1 induced apoptosis ; moreover , the Smad 3 mutant was more efficient than the Smad 2 mutant . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The endogenous ratio of Smad 2 and Smad 3 influences the cytostatic function of Smad 3 . ^^^ Although Smad 2 and Smad 3 , critical transcriptional mediators of transforming growth factor beta ( TGF beta ) signaling , are supposed to play a role in the TGF beta cytostatic program , it remains unclear whether TGF beta delivers cytostatic signals through both Smads equally or through either differentially . ^^^ Here , we report that TGF beta cytostatic signals rely on a Smad 3 , but not a Smad 2 , dependent pathway and that the intensity of TGF beta cytostatic signals can be modulated by changing the endogenous ratio of Smad 3 to Smad 2 . ^^^ Depleting endogenous Smad 3 by RNA interference sufficiently interfered with TGF beta cytostatic actions in various TGF beta sensitive cell lines , whereas raising the relative endogenous ratio of Smad 3 to Smad 2 , by depleting Smad 2 , markedly enhanced TGF beta cytostatic response . ^^^ Consistently , Smad 3 activation and its transcriptional activity upon TGF beta stimulation were facilitated in Smad 2 depleted cells relative to controls . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Functionally , we determined interaction of Fussel 18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF beta signaling . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGF beta 1 is a key cytokine in the process of fibrogenesis , using intracellular signaling pathways involving Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
A multimerized SBE promoter responsive to TGF beta 1 signaling is highly activated by Smad 3 but not by the closely related Smad 2 . ^^^ Intriguingly , myocardin ( Myocd ) , a known CArG box dependent serum response factor coactivator , participates in Smad 3 mediated TGF beta 1 signaling and synergistically stimulates Smad 3 induced SBE promoter activity independent of the CArG box ; no such synergy is seen with Smad 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The differential role of Smad 2 and Smad 3 in the regulation of pro fibrotic TGFbeta 1 responses in human proximal tubule epithelial cells . ^^^ In the present study we have investigated the distinct contributions of Smad 2 and Smad 3 to expression of CTGF , E cadherin , alpha SMA ( alpha smooth muscle actin ) and MMP 2 ( matrix metalloproteinase 2 ) in response to TGFbeta 1 treatment in an in vitro culture model of HKC 8 ( transformed human PTECs ) . ^^^ RNA interference was used to achieve selective and specific knockdown of Smad 2 and Smad 3 . ^^^ TGFbeta 1 induced increases in CTGF and decreases in E cadherin expression were Smad 3 dependent , whereas increases in MMP 2 expression were Smad 2 dependent . ^^^ Increases in alpha SMA expression were dependent on both Smad 2 and Smad 3 and were abolished by combined knockdown of both Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transforming growth factor beta activation of phosphatidylinositol 3 kinase is independent of Smad 2 and Smad 3 and regulates fibroblast responses via p 21 activated kinase 2 . ^^^ In the current study , we determined that TGF beta receptor signaling activates phosphatidylinositol 3 kinase ( PI3K ) in several fibroblast but not epithelial cultures independently of Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Using small interference RNA ( siRNA ) , the role of Smad 2 and Smad 3 in TGF beta stimulation of human lung fibroblast contraction of collagenous matrix and induction of alpha SMA and the role of alpha SMA in contraction were assessed . ^^^ HFL 1 cells were transfected with Smad 2 , Smad 3 or control siRNA , and cultured in floating Type 1 collagen gels + / TGF beta 1 . ^^^ TGF beta 1 augmented gel contraction in Smad 2 siRNA and control siRNA treated cells , but had no effect in Smad 3 siRNA treated cells . ^^^ Similarly , TGF beta 1 upregulated alpha SMA in Smad 2 siRNA and control siRNA treated cells , but had no effect on Smad 3 siRNA treated cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In the first , Smad 3 ( but not Smad 2 ) activates expression of Xlim 1 in a direct fashion . ^^^ As well as revealing the function of Smicl in the early embryo , our work yields important new insight in the regulation of Chordin and identifies functional differences between the activities of Smad 2 and Smad 3 in the Xenopus embryo . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Transduction of TGF beta signaling depends on activation of Smad 2 and Smad 3 by heteromeric complexes of ligand specific receptors . ^^^ Mice lacking Smad 3 show accelerated wound healing , whereas the biological significance of Smad 2 mediated TGF beta signaling in wound healing remains unknown . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad 2 or Smad 3 overexpression and BMP blockade abrogate accelerated maturation in Smad 3 / chondrocytes . ^^^ Recombinant noggin or retroviral vectors expressing Smad 2 or Smad 3 were added to the cultures . ^^^ Smad 3 / chondrocytes lacked compensatory increases in Smad 2 , Smad 4 , TGFRII , Sno , or Smurf 2 and had reduced expression of TGF beta 1 and TGFRI . ^^^ Overexpression of both Smad 2 and Smad 3 blocked spontaneous maturation in Smad 3 deficient chondrocytes . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Paclitaxel markedly suppressed Smad 2 and Smad 3 phosphorylation and collagen deposition in SSc grafts . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Smad family proteins Smad 2 and Smad 3 are activated by transforming growth factor beta ( TGF beta ) / activin / nodal receptors and mediate transcriptional regulation . ^^^ Although differential functional roles of Smad 2 and Smad 3 are apparent in mammalian development , the relative functional roles of Smad 2 and Smad 3 in postnatal systems remain unclear . ^^^ We used Cre / loxP mediated gene targeting for hepatocyte specific deletion of Smad 2 ( S2HeKO ) in adult mice and generated hepatocyte selective Smad2 / Smad3 double knockouts by intercrossing AlbCre / Smad2 ( f / f ) ( S2HeKO ) and Smad 3 deficient Smad3ex8 / ex8 ( S3KO ) mice . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We examined the immunohistochemical localization of inhibin / activin alpha subunit , betaA subunit , activin A , and activin receptor types IA , IB , IIA , IIB , Smad 2 , Smad 3 and Smad 4 using an avidin biotin peroxidase complex technique . ^^^ We observed positive immunoreactive staining in the cytoplasm and nucleus with the antibodies against the Smad 2 , Smad 3 and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Furthermore , we demonstrate that NS5A protein abrogated the phosphorylation of Smad 2 and the heterodimerization of Smad 3 and Smad 4 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Interestingly , Smad 2 and Smad 3 play opposite roles in regulating snoN expression in both fibroblasts and epithelial cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Dominant negative RhoA blocked nuclear translocation of Smad 2 and Smad 3 because of the inhibition of phosphorylation of both Smads and inhibited Smad dependent SBE promoter activity , whereas constitutively active RhoA significantly enhanced SBE promoter activity . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The expression levels of Smad 2 , Smad 3 and Smad 4 proteins were determined by immunoblotting . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Treatment with TGF beta resulted in activation of Smad 2 and Smad 3 in SCC cells , but had no effect on their proliferation or viability . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Further study showed that atRA inhibited phosphorylation of Smad 2 and Smad 3 and increased Smad 7 expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In agreement , pretreatment of MCF 7 cells with 17 beta estradiol resulted in a reduced phosphorylation of Smad 2 and Smad 3 as well as a diminished Smad 2 and Smad 3 gene reporter activity in response to TGF beta . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We show that the mammalian PDPs are important in dephosphorylation of BMP activated Smad 1 but not TGF beta activated Smad 2 or Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TGFB 1 , acting via SMAD 2 and SMAD 3 , antagonized the degradation of CCND 2 protein by blocking its phosphorylation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Asiaticoside was determined to induce the phosphorylation of both Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
This study examined Smad 2 and Smad 3 dependent transcription in 12 human head and neck squamous cell carcinoma ( HNSCC ) cell lines following treatment with transforming growth factor beta 1 ( TGF beta 1 ) . ^^^ A markedly elevated level of TGF beta 1 induced Smad 3 signalling was observed in one cell line ( H 357 ) , whilst four cell lines ( BICR 31 , H 314 , BICR 56 , BICR 19 ) demonstrated absence of Smad 3 dependent transcription that correlated with loss of TGF beta 1 growth inhibition ; TGF beta 1 induced Smad 2 dependent transcription was retained in two of these cell lines ( H 314 , BICR 31 ) . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
CER 1 ( Cerberus 1 ) and GREM 3 ( CKTSF1B3 or CER 2 ) inhibit NODAL signaling through ACVR1B ( ALK 4 ) or ACVR1C ( ALK 7 ) to SMAD 2 or SMAD 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Dominant negative Smad 2 , Smad 3 , and Smad 4 blocked ALK 7 ca regulated Xiap and Bax expression and caspase 3 activation . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The SMAD 3 level was not altered by the Smad 2 siRNA transfection . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Indeed , compared to WT mice , the amounts of total and phosphorylated Smad 2 and Smad 3 were decreased with a reciprocal increase in the amount of Smad 7 in skin wound sites of IL 1ra deficient mice . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
After 8 weeks , we examined the following indexes : the ratio of ventricular weight to body weight ( VW / BW ) , left ventricular end diastolic dimension ( LVDd ) , ejection fraction ( EF ) , fractional shortening ( FS ) , ratio of E wave to A wave velocity , collagen of noninfarcted zone , the mRNA expression of TGFbeta ( 1 ) , Smad 2 , and Smad 3 by RT PCR in noninfarcted zone , the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot . ^^^ The mRNA expression of TGFbeta ( 1 ) , Smad 2 , and Smad 3 ( 0 . 700 + / 0 . 045 , 0 . 959 + / 0 . 037 and 0 . 850 + / 0 . 051 ) increased in placebo group compared with that in control group ( P < 0 . 01 ) . ^^^ The expression of Smad 2 and Smad 3 protein increased in placebo group compared with that in control group ( P < 0 . 01 ) . ^^^ ACEI and ARB treatment prevents ventricular remodeling by inhibiting expression of Smad 2 and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Finally , activation of Smad 3 but not Smad 2 was a key and necessary mechanism of Ang 2 induced vascular fibrosis because Ang 2 induced Smad3 / 4 promoter activities and collagen matrix expression was abolished in VSMCs null for Smad 3 but not Smad 2 . ^^^ Activation of Smad 3 but not Smad 2 is a key mechanism by which Ang 2 mediates arteriosclerosis . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
It also binds to chromatin associated proteins and transcriptional regulators , including the R Smads , Smad 1 , Smad 2 , and Smad 3 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Here we show that in isolated human NK cells , proinflammatory monokines antagonize antiinflammatory TGF beta signaling by downregulating the expression of the TGF beta type 2 receptor , and its signaling intermediates SMAD 2 and SMAD 3 . ^^^ In contrast , TGF beta utilizes SMAD 2 , SMAD 3 , and SMAD 4 to suppress IFN gamma and T BET , a positive regulator of IFN gamma . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In this issue of Cell , Lin et al . ( 2006 ) answer one of the long standing questions in the TGFbeta field by identifying a phosphatase , PPM1A , that directly dephosphorylates Smad 2 and Smad 3 to limit their activation . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Trx SARA bound specifically to Smad 2 and Smad 3 and inhibited both TGF beta induced reporter gene expression and epithelial to mesenchymal transition in NMuMG murine mammary epithelial cells . ^^^ The key mode of action of Trx SARA was to reduce the level of Smad 2 and Smad 3 in complex with Smad 4 after TGF beta 1 stimulation , a mechanism of action consistent with the preferential binding of SARA to monomeric Smad protein and Trx SARA mediated disruption of active Smad complexes . . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
In this study , we investigated the expression of Smad 2 and Smad 3 , which are specific intracellular mediators of TGF beta signaling . ^^^ METHODS : Immunohistochemical staining with anti phosphorylated Smad 2 ( P Smad 2 ) polyclonal antibody , anti Smad 2 monoclonal antibody , and anti Smad 3 polyclonal antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC . ^^^ There was no significant correlation between expression of Smad 2 or Smad 3 and clinicopathologic characteristics . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
TSAd interacts with Smad 2 and Smad 3 . ^^^ Using yeast two hybrid , co immunoprecipitation , and GST pull down assays we identified T cell SH 2 adapter ( TSAd ) as a protein that interacts with Smad 2 and Smad 3 . ^^^ Interestingly , we also found that both Smad 2 and Smad 3 interact with the Lck type 1 SH 2 domain , but not the PI3K type 3 SH 2 domain . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The functions of activin , a member of TGF beta superfamily , in ovarian clear cell adenocarcinoma remain unsolved , although we recently found that inhibin betaA subunit , activin A , activin receptor type IA , type IB , type IIA , type IIB , Smad 2 , Smad 3 and Smad 4 were localized in tumor cells of the ovarian clear cell adenocarcinoma tissue by immunohistochemistry . ^^^ The expression of activin receptor type IA , IB , IIA , IIB , Smad 2 , Smad 3 and Smad 4 was observed in JHOC 5 cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
An increased proliferation and reduced SMAD 2 , SMAD 3 , and SMAD 4 mRNA expression were observed in both TGF beta 1 and ActA knockdown cells . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Lung homogenates were analyzed by enzyme linked immunosorbent assay ( ELISA ) for cytokines [ tumor necrosis factor alpha ( TNFalpha ) , interleukin ( IL ) 1beta , TGFbeta 1 , oncostatin M ( OSM ) , IL 10 , and interferon gamma ( IFNgamma ) ] and the chemokine MCP 1 and by Western blot for Smad 2 , Smad 3 , and Smad 7 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
Although c Abl activation by TGF beta is independent of Smad 2 or Smad 3 , it is prevented by inhibitors of phosphatidylinositol 3 kinase or PAK 2 . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
METHODS : The authors examined the expression of downstream components of the TGFbeta receptor , including Smad 2 , Smad 3 , Smad 4 , and Smad 7 , and the effect of TGFbeta 1 treatment on the phosphorylation of Smad 2 and the nuclear translocation of Smad 2 and Smad 3 by using 10 glioma cell lines and the A 549 cell line , which is sensitive to TGFbeta mediated growth inhibition . ^^^ Expression of the Smad 2 and Smad 3 proteins was lower in the glioma cell lines than in the A 549 cell line and in normal astrocytes . ^^^ Seven of the 10 glioma cell lines exhibited lower levels of nuclear translocation of Smad 2 and Smad 3 , and two cell lines that expressed very low levels of Smad 3 protein showed no nuclear translocation . ^^^ Overall , the expression of the Smad 2 and Smad 3 proteins was low in the glioma cell lines , the phosphorylation and nuclear translocation of Smad 2 and Smad 3 were impaired , and the TGFbeta receptor signal did not affect the expression of the SnoN , p 21 , p 15 , cyclin D 1 , and CDK 4 proteins . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
We also found that TSA , a HDAC inhibitor that stimulates histone acetylation of the SM22alpha locus , further enhances the transactivational activity of Smad 2 , Smad 3 and Smad 4 , and relieves the inhibitory effect of Smad 6 , Smad 7 , and the dominant negative mutants of Smads . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
The production of collagen and the mRNA expression of transforming growth factor ( TGF ) beta 1 , SMAD 2 , SMAD 3 , SMAD 4 , SMAD 7 and type 1 procollagen alpha 1 , alpha 2 in fibroblasts were investigated by colorimetry or real time polymerase chain reaction . ^^^ The mRNA expression of TGF beta 1 , SMAD 2 , SMAD 3 , SMAD 4 , SMAD 7 and procollagen 1 was significantly up regulated after treatment with a 585 nm flashlamp pumped pulsed dye laser with a fluence of 3 J / cm ( 2 ) ( P < 0 . 001 ) . ^^^ No significant difference of mRNA expression of SMAD 2 , SMAD 3 , SMAD 4 , SMAD 7 and type 1 procollagen was found between controls and fibroblasts treated with pulsed dye laser with a fluence of 4 J / cm ( 2 ) ( P > 0 . 05 ) . ^^^ CONCLUSIONS : Lower fluence ( 3 J / cm ( 2 ) ) pulsed dye laser increased the collagen production in fibroblasts by up regulating TGF beta 1 , SMAD 2 , SMAD 3 , SMAD 4 , SMAD 7 and type 1 procollagen mRNA expression . ^^^
Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and P84022	Pubmed	SVM Score :0.0
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