Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.70259754
Similar carboxy terminal serines in Smad 2 are required for its phosphorylation and association with DPC 4 in response to TGF beta , indicating the generality of this process of Smad activation . 0.70259754^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.94878105
For example , Smad 2 is phosphorylated by the TGF beta type 1 receptor upon ligand binding , forms a heteromer with Smad 4 , and then translocates into the nucleus where it activates transcription . 0.94878105^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.86105091
Phosphorylation at both sites is required to mediate association of Smad 2 with Smad 4 in mammalian cells , while in yeast , Smad 2 interacts directly with Smad 4 and does not require phosphorylation . 0.86105091^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.62336792
Consistent with such a mechanism , Smad 4 interacts functionally with both Smad 1 and 2 to potentiate their signaling activities , and a dominant negative variant of Smad 4 can inhibit both activin / BVg1 and BMP 2 / 4 mediated signaling Finally , we demonstrate that an activin / BVg1 dependent transcriptional complex contains both Smad 2 and Smad 4 and thereby provides a physical basis for the functional involvement of both Smads in TGF beta dependent transcriptional regulation . 0.62336792^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.59792626
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 . 0.59792626^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.53775916
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 . 0.53775916^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.86400828
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 . 0.86400828^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.64456889
We conclude that LMC was induced because C terminal phosphorylated smad 2 lost its ability to bind to smad 4 , and consequently could not accumulate in the nucleus . 0.64456889^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.73075382
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 . 0.73075382^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 . . ^^^ 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 . ^^^ Low levels of Smad 4 mRNA coinjected with Smad 1 or Smad 2 mRNA also synergized to induce ventral or dorsal mesoderm , respectively . ^^^ 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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The MAD ( mothers against decapentaplegic ) related genes , Smad 2 ( former name MADR 2 or JV 18 1 ) and Smad 4 ( former name DPC 4 ) , have been identified on chromosome 18q21 . 1 . ^^^ MAD related genes on 18q21 . 1 , Smad 2 and Smad 4 , are altered infrequently in esophageal squamous cell carcinoma . ^^^ We analyzed 30 primary esophageal squamous cell carcinomas ( ESCC ) and 7 cell lines derived from ESCC for intragenic mutations and loss of heterozygosity ( LOH ) of the Smad 2 and Smad 4 genes . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Previously , Smad 4 and Smad 2 were shown to be mutated in human cancers . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Mutations increasing autoinhibition inactivate tumour suppressors Smad 2 and Smad 4 . ^^^ Smad 2 and Smad 4 are related tumour suppressor proteins , which , when stimulated by the growth factor TGF beta , form a complex to inhibit growth . ^^^ The effector function of Smad 2 and Smad 4 is located in the conserved carboxy terminal domain ( C domain ) of these proteins and is inhibited by the presence of their amino terminal domains ( N domain ) . ^^^ This inhibitory function of the N domain is shown here to involve an interaction with the C domain that prevents the association of Smad 2 with Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
This leads to Smad 2 association with Smad 4 , translocation to the nucleus , and regulation of transcriptional responses . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ We report here that DPC 4 is essential for the function of Smad 1 and Smad 2 in pathways that signal mesoderm induction and patterning in Xenopus embryos , as well as antimitogenic and transcriptional responses in breast epithelial cells . ^^^ DPC 4 associates with Smad 1 in response to BMP and with Smad 2 in response to activin or TGF beta . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 2 is closely linked to DPC 4 on chromosome 18q21 . 1 , a region often deleted in human cancers . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Activins are growth factors that act primarily through Smad 2 , possibly in partnership with Smad 4 , which forms heteromeric complexes with different ligand specific SMADs after activation . ^^^ We now report that Smad 4 is present in ARF , and that FAST 1 , Smad 4 and Smad 2 co immunoprecipitate in a ligand regulated fashion . ^^^ In a yeast two hybrid assay , the FAST 1 carboxy terminus interacts with Smad 2 but not Smad 4 . ^^^ Deletion mutants of the FAST 1 carboxy terminus that still participate in ligand regulated Smad 2 binding no longer associated with Smad 4 or ARF . ^^^ These results indicate that Smad 4 stabilizes a ligand stimulated Smad 2 FAST 1 complex as an active DNA binding factor . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
C2C12 cells expressed Smad 1 , Smad 2 , Smad 4 , and Smad 5 mRNAs , and expression levels were not altered by treatment with BMP 2 or TGF beta 1 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
TGF beta receptor mediated signalling through Smad 2 , Smad 3 and Smad 4 . ^^^ Smad 4 is distantly related to Smads 2 and 3 , and forms a heteromeric complex with Smad 2 after TGF beta or activin stimulation . ^^^ Dominant negative Smad 3 inhibited the transcriptional synergistic response by Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 4 ( homolog of human DPC 4 ) and Smad 2 ( homolog of human JV 18 1 ) : candidates for murine lung tumor resistance and suppressor genes . ^^^ Smad 4 ( homolog of human DPC 4 ) and Smad 2 ( homolog of human JV 18 1 ) : candidates for murine lung tumor resistance and suppressor genes . ^^^ Thus , in this study we found no evidence that either Smad 4 or Smad 2 represents the Par 2 lung tumor resistance locus or is a lung tumor suppressor gene in the B6CF1 mice . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Phosphorylation of Ser 465 and Ser 467 in the C terminus of Smad 2 mediates interaction with Smad 4 and is required for transforming growth factor beta signaling . ^^^ After activation of TGF beta receptors , Smad 2 and Smad 3 become phosphorylated and form heteromeric complexes with Smad 4 . ^^^ Mutation of Ser 465 and Ser 467 in Smad 2 abrogated complex formation of this mutant with Smad 4 and blocked the nuclear accumulation not only of Smad 2 , but also of Smad 4 . ^^^ Thus , heteromeric complex formation of Smad 2 with Smad 4 is required for nuclear translocation of Smad 4 . ^^^ Moreover , peptides from the C terminus of Smad 2 containing phosphorylated Ser 465 and Ser 467 were found to bind Smad 4 in vitro , whereas the corresponding unphosphorylated peptides were less effective . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 5 homologs Smad 2 and DPC 4 have recently been linked to human cancer . ^^^ RT PCR sequencing analysis of the HL 60 Smad5 remaining allele ruled out the functional inactivation of the gene analogous to that occurring in the Smad 5 homologs DPC 4 and Smad 2 in cases of pancreatic and colorectal cancers . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Smad 2 shows considerable sequence similarity with Smad 4 and cooperates with it in the growth inhibitory TGF beta pathway . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ Moreover , overexpression of Smad 4 prevented Smad 2 from forming a homo oligomer . ^^^ These findings suggest that Smad 2 may form a homotrimer , or heterotrimers with Smad 4 , which are probably composed of two and one , or one and two molecules of Smad 2 and Smad 4 , respectively , depending on the amount of each protein . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
We demonstrate by both a mammalian two hybrid and a biochemical approach that human Smad 2 and Smad 4 , two essential Smad proteins involved in mediating TGF beta transcriptional responses in endothelial and other cell types , can functionally interact with the transcriptional coactivator CREB binding protein ( CBP ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 4 is not required for nuclear translocation of Smads 1 or 2 , or for association of Smad 2 with a DNA binding partner , the winged helix protein FAST 1 . ^^^ Receptor activated Smad 2 takes Smad 4 into the nucleus where they form a complex with FAST 1 that requires these three components to activate transcription . ^^^ Smad 4 contributes two functions : Through its amino terminal domain , Smad 4 promotes binding of the Smad2 / Smad4 / FAST 1 complex to DNA ; through its carboxy terminal domain , Smad 4 provides an activation function required for Smad 1 or Smad 2 to stimulate transcription . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Abrogation of Smad 4 ( DPC 4 ) , the downstream mediator of Smad 3 and Smad 2 proteins , with antisense oligodeoxynucleotide , also resulted in increased branching morphogenesis . ^^^ Abrogation of Smad 3 and Smad 2 or of Smad 4 gene expression positively regulates murine embryonic lung branching morphogenesis in culture . ^^^ Our results demonstrate , for the first time , that abrogation of Smad 2 and Smad 3 or of Smad 4 gene expression stimulated early mouse embryonic lung branching morphogenesis in culture , possibly through reversing the negative influence of endogenous TGF beta signaling upon lung branching morphogenesis . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
The aim of our study was to determine the presence of alterations in the main putative components of the TGF beta inhibitory signaling pathways ( p 15 , Smad 4 , Smad 2 , TGFbeta RII , CDC25A ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
FAST 2 binds to a sequence in the gsc promoter , but efficient transcriptional activation and assembly of a DNA binding complex of FAST 2 , Smad 2 , and Smad 4 requires an adjacent Smad 4 site . ^^^ Inhibitory activity is conferred by the MH 1 domain , which unlike that of Smad 2 , binds to the Smad 4 site . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The size of this region is less than 1 Mb , and the coding exons of three candidate tumor suppressor genes , Smad 2 , Smad 4 , and DCC , were mapped outside the region . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In contrast , activin induced phosphorylation of Smad 2 , association with Smad 4 , and induction of the activin response element from the Xenopus Mix . 2 gene . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 2 overexpression enhances Smad 4 gene expression and suppresses CBFA 1 gene expression in osteoblastic osteosarcoma ROS17 / 2 . 8 cells and primary rat calvaria cells . ^^^ 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 . ^^^ These data indicate that Smad 2 regulates Smad 4 specifically and that CBFA 1 gene is one of the downstream targets of Smad2 . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Among the transducers of the transforming growth factor ( TGF ) beta / bone morphogenetic protein ( BMP ) receptor signaling proteins , Smad 4 and Smad 1 act together in BMP 2 / 4 signaling pathways , and Smad 4 and Smad 2 act in TGF beta / activin signaling . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
FAST 2 also interacts directly with Smad 2 , a cytoplasmic protein which is translocated to the nucleus in response to TGF beta , and forms a multimeric complex with Smad 2 and Smad 4 on the activin response element , a high affinity binding site for FAST 1 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
At least two different Smads , Smad 2 and Smad 4 ( DPC 4 ) , have been implicated in human cancer and appear to have tumour suppressor functions . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Mutation analysis of transforming growth factor beta type 2 receptor , Smad 2 , and Smad 4 in hepatocellular carcinoma . ^^^ Mutations in the transforming growth factor beta type 2 receptor ( TGFbetaRII ) , Smad 2 , and Smad 4 genes have been detected in several human cancers . ^^^ These results suggest that mutations of the TGFbetaRII , Smad 2 , and Smad 4 genes are rare , and that genetic instability is uncommon in human hepatocellular carcinoma . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 . ^^^ In contrast , Smad 2 ( wt ) , Smad2Deltaexon3 , and Smad 3 efficiently formed ARE binding complexes with Smad 4 and FAST 1 , although Smad 2 ( wt ) did not directly bind to ARE . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
TGFB receptor activation results in SMAD 2 and SMAD 3 phosphorylation , which then form heteromeric complexes with SMAD 4 . ^^^ 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 . ^^^ These results suggest that functional abrogation of SMAD 2 or SMAD 3 and increased expression of SMAD 6 or SMAD 7 are infrequent in pancreatic carcinomas and further stress the particular importance of SMAD 4 inactivation in pancreatic carcinogenesis . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Using two point mutations of Smad 2 previously identified in colorectal carcinomas , we show that Smad 2 ushers Smad 4 to the nucleus to form a transcriptional activation complex with the nuclear DNA binding protein FAST 1 and that the mutant proteins interact normally with FAST 1 but fail to recruit Smad 4 into the nucleus . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Following TGFbeta receptor mediated phosphorylation and association with Smad 4 , Smad 2 moves into the nucleus , binds to target promoters in association with DNA binding cofactors , and recruits coactivators such as p300 / CBP to activate transcription . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 , Smad 4 , Smad 6 and Smad 7 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
To clarify the target of 18qLOH , mutation of Smad 4 and Smad 2 genes was analysed in 176 colorectal tumors with different stages , including liver metastasis , from 111 sporadic , 52 familial adenomatous polyposis ( FAP ) and nine hereditary nonpolyposis colorectal cancer ( HNPCC ) patients . ^^^ 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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Smad 2 , Smad 4 , Smad 5 , Smad 6 and Smad 7 were not identified in eccrine sweat gland epithelia . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Despite the expression of Smad 5 from gastrulation onwards , and in contrast to knockouts of Smad 2 and Smad 4 , Smad 5 only becomes essential later in extraembryonic and embryonic development . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Activation of Smad 2 by active MEKK 1 results in enhanced Smad 2 Smad4 interactions , nuclear localization of Smad 2 and Smad 4 , and the stimulation of Smad protein transcriptional coactivator interactions in endothelial cells . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Chromosomal arm 18q harbors the DPC 4 , SMAD 2 , and DCC genes and is suspected on the basis of high frequencies of allelic loss to harbor additional tumor suppressor genes . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
Recently , three candidate tumor suppressor genes , SMAD 2 ( MADR2 / JV18 1 ) , SMAD 4 ( DPC 4 ) , and DCC , were identified in chromosome band 18q21 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Constitutive activation of the p 38 pathway in the absence of TGF beta induced the transcriptional activation , which was enhanced synergistically by coexpression of Smad 2 and Smad 4 and was inhibited by expression of the C terminal truncated , dominant negative Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Smad 2 and Smad 4 gene mutations in hepatocellular carcinoma . ^^^ We studied 35 HCC and non tumour liver tissues for possible mutations in Smad 2 and Smad 4 genes . ^^^ Three tumours displayed somatic mutations ; two in Smad 4 ( Asp332Gly and Cys401Arg ) and one in Smad 2 ( Gln407Arg ) genes . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 . ^^^ CONCLUSIONS : Smad 2 , Smad 3 , and Smad 4 are present and activated by TGF beta 1 in human mesangial cells . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Activated TbetaRI phosphorylates Smad 2 , which then heterodimerizes with Smad 4 , translocates into the nucleus , and subsequently effects gene transcription . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
FAST 1 has been shown to associate with Smad 2 and Smad 4 , transducers of TGFbeta superfamily signals , in response to stimulation by several TGFbeta superfamily ligands . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
The SnoN oncoprotein was found to interact with Smad 2 and Smad 4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N CoR . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In order to elucidate the functional importance of the H3 / 4 loop , we prepared chimeric constructs of Smad 4 containing the region corresponding to the alpha helix 3 , H3 / 4 loop and alpha helix 4 of different Smads , including a chimera containing that of Smad 2 ( Smad 4 HL2 ) . ^^^ However , co transfection of Smad 2 with Smad 4 HL2 did not induce a further increase in the activation of p3TP Lux . ^^^ Smad 4 HL2 did not induce the activation of pAR 3 Lux , which contains FAST 1 binding sites and is activated by a complex composed of FAST 1 , Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Here , we showed that TGF beta phosphorylated Smad 2 and induced interaction between Smad 2 and Smad 4 in primary T cells and the Jurkat T cell line . ^^^ Interestingly , ligation of the T cell receptor ( TCR ) / CD3 complex with anti CD 3 mAb also phosphorylated Smad 2 , but failed to induce interaction between Smad 2 and Smad 4 in the Jurkat T cell line . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Since a high incidence of 18q21 AI was detected in the superficial depressed cases , we further screened for alterations in Smad 2 , Smad 4 and DCC . ^^^ Smad 4 alterations were only detected in 1 of the 13 superficial depressed and 3 of the 17 protruding cases , while Smad 2 and DCC alterations were not detected in any case examined . ^^^ These data suggest that the carcinogenetic pathways of protruding and superficial depressed colorectal cancers are different , and that alterations of tumor suppressor gene ( s ) located on 18q21 other than Smad 2 , Smad 4 and DCC might be associated with most superficial depressed colorectal cancers . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
DNA cloning and chromosomal mapping of rat Smad 2 and Smad 4 and their expression in cultured rat articular chondrocytes . ^^^ We report here the entire sequences of rat Smad 2 and Smad 4 which have not been identified yet . ^^^ The predicted amino acid sequences of rat Smad 2 and Smad 4 are highly conserved among rat , human and mouse . ^^^ Since both Smad 2 and Smad 4 are essential factors for TGF beta signalling , we examined their expression and regulation in cultured articular chondrocytes . ^^^ Northern blot analysis showed that TGF beta 1 significantly increased the mRNA level of Smad 2 but not of Smad 4 in a dose and time dependent manner , suggesting that the augmentation of TGF beta 1 action is caused by increasing the expression of the downstream signalling molecule . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Similarly , expression of individual Smad proteins had only a modest effect on reporter gene activity , but the combination of Smad 2 and Smad 4 strongly stimulated transcription . ^^^ In contrast , green fluorescence protein Smad 4 remained localized to the cytoplasm unless it was coexpressed with Smad 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Three candidate tumor suppressor genes , DCC , Smad 4 and Smad 2 have been identified in this chromosome region . ^^^ The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad 4 and Smad 2 genes during colorectal and pancreatic distal dissemination . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGFbeta signaling , deregulation of SnoN or Ski expression leads to total inhibition of TGFbeta signaling and of the tumor suppressors Smad 2 and Smad 4 , which can explain the role of SnoN and Ski as oncogenes . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
The common region of AI at 18q21 . 1 includes the DCC gene but not the Smad 2 and Smad 4 genes . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In TGFbeta pathways LOH positive tumours inactivated SMAD 2 ( similar to mother against decapentaplegic drosophilia ) or SMAD 4 , whereas in MSI positive tumours the TGFbeta type 2 receptor is frequently deleted . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Expression of left ventricular ( LV ) receptor activated ( Smad 2 ) and common mediator ( Smad 4 ) Smads from control ( F 1 beta strain ) hamsters , non treated cardiomyopathic ( CMP ) , and losartan treated CMP animals was assessed . ^^^ In LV preparations containing nuclear extract , elevated Smad 2 and Smad 4 protein expression was noted in cardiomyopathic hearts vs . controls . ^^^ Losartan treatment of late stage CMP hamsters was associated with a significant reduction in Smad 2 and a modest reduction of Smad 4 protein expression vs . untreated CMP samples . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Using Northern blot analysis , Smad 2 and Smad 4 mRNAs were also observed in JEG 3 cells . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Although no detectable change was induced in Smad 4 mRNA in OVCAR 3 , Smad 2 mRNA levels were increased during 48 h treatment with activin A ( 50 ng ml ( 1 ) ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Mutations in the tumor suppressors Smad 2 and Smad 4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin proteasome pathway . ^^^ Smad 2 and Smad 4 are important for transcriptional and antiproliferative responses to TGF beta , and their inactivation in human cancers indicates that they are tumor suppressors . ^^^ A missense mutation at a conserved arginine residue in the amino terminal MH 1 domain of both Smad 2 and Smad 4 has been identified in tumors from patients with colorectal and pancreatic cancers , respectively . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Activation of TGF beta receptor type 1 ( RI ) and RII by TGF beta induces nuclear translocation of Smad proteins including Smad 2 and Smad 4 that have been originally identified as tumour suppressor genes . ^^^ In this study , we analysed genetic mutations of TGF beta RII , Smad 2 and Smad 4 in these oesophageal carcinoma tissues and established 16 cell lines . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Heterogeneities in the biological and biochemical functions of Smad 2 and Smad 4 mutants naturally occurring in human lung cancers . ^^^ In the study presented here , we characterized the biological and biochemical functions of six Smad 2 and Smad 4 mutants , which we previously identified in human lung cancers . ^^^ All mutant Smad 2 and Smad 4 were in fact found to be defective in transmitting growth inhibitory signals originating from TGF beta and incapable of activating Smad / hFAST 1 mediated transcription . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Frequent inactivating mutations of SMAD 4 , or less common somatic mutations of SMAD 2 seen in solid tumors , suggest that these genes have a suppressor function . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
METHODS : Paraffin embedded tissue sections containing tumor and adjacent nonneoplastic parenchyma were analyzed by immunohistochemistry for the expression of TbetaR type 2 ( TbetaR 2 ) and Smad 2 , Smad 4 , Smad 6 , and Smad 7 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Similarly , homologues for mouse Ctse , Pcdh 13 , Cspg 5 and Myo 10 genes and homologues for rat Smad 2 ( Madh 2 ) and Smad 4 ( Madh 4 ) genes were assigned to Chinese hamster chromosomes ( CGR ) 5q28 , 2q17 , 4q26 , 2p29 > p 27 , 2q112 > q 113 and 2q112 > q 113 , respectively . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
For the first time , mutations in the Smad 2 and Smad 4 genes were analyzed in relation to human ovarian cancer . ^^^ Gene mutations of TGF beta RI , TGF beta RII , Smad 2 , and Smad 4 were analyzed using specific primers by PCR single strand conformational polymorphism ( SSCP ) , and the results revealed a frameshift mutation at codons 276 277 ( CTCTGG > CTGCGTGG ) in exon 5 of TGF beta RI in 10 of 32 tumor samples ( 31 . 3 % ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Three candidate tumour suppressor genes , DCC , SMAD 4 and SMAD 2 , map to this region . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Smad 2 , Smad 3 and Smad 4 cooperate with Sp 1 to induce p 15 ( Ink4B ) transcription in response to TGF beta . ^^^ In this study , we demonstrate that p 15 ( Ink4B ) induction was mediated by a TGF beta induced complex of Smad 2 , Smad 3 , Smad 4 and Sp 1 . ^^^ Interference with , or deficiency in , Smad 2 , Smad 3 or Smad 4 functions also reduced or abolished the TGF beta dependent p 15 ( Ink4B ) induction , whereas the absence of Sp 1 reduced the basal and TGF beta induced p 15 ( Ink4B ) transcription . ^^^ 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 . ^^^ Our data demonstrate the physical interactions and functional cooperativity of Sp 1 with a complex of Smad 2 , Smad 3 and Smad 4 in the induction of the p 15 ( Ink4B ) gene . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^ 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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ We propose that , upon TGF beta signaling , complex formation between Smad 4 and activated Smad 2 or 3 leads to nuclear accumulation of Smad 4 through inhibition of its nuclear export . ^^^ We demonstrate that after prolonged TGF beta signaling Smad 2 becomes dephosphorylated and Smad 2 and Smad 4 accumulate back in the cytoplasm . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Mutations of the Smad 2 and Smad 4 genes in lung adenocarcinomas induced by N nitrosobis ( 2 hydroxypropyl ) amine in rats . ^^^ Mutations of the Smad 2 and Smad 4 genes , identified as mediators of the transforming growth factor beta pathway , were investigated in lung adenocarcinomas induced by N nitrosobis ( 2 hydroxypropyl ) amine ( BHP ) in rats . ^^^ Total RNA was extracted from 12 adenocarcinomas , and mutations in Smad 2 and Smad 4 were investigated by reverse transcription polymerase chain reaction restriction single strand conformation polymorphism analysis followed by sequencing analysis . ^^^ These results suggest that mutations of Smad 2 and Smad 4 may play roles in a limited fraction of lung adenocarcinomas induced by BHP in rats . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Losartan administration ( 8 wk , 15 mg . kg ( 1 ) . day ( 1 ) ) normalized total Smad 2 overexpression in infarct scar and remnant heart tissue and normalized Smad 4 in infarct scar . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
By glutathione Sepharose affinity purification , ATP treatment , DEAE Sepharose and hydroxylapatite columns , expressed Smads were purified to near homogeneity as judged by SDS PAGE ; protein recovery was ca . 1 mg / l culture for Smad 2 and 100 microg / l culture for Smad 4 . ^^^ The purified Smad proteins had three known in vitro activities : Smad 2 phosphorylation by TGF beta receptor complexes immunoprecipitated from COS 7 cells , Smad 4 binding to Smad binding DNA element , and Smad 2 interaction with calmodulin . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad proteins are effector molecules that transmit signals from the receptors for the transforming growth factor beta ( TGF beta ) superfamily to the nucleus ; of the Smad proteins , Smad 2 and Smad 4 are essential components for mouse early embryogenesis . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ Loss of SMAD 2 or SMAD 4 results in related phenotypes : the mutants fail to form an organized egg cylinder , lack mesoderm required for gastrulation and die prior to E8 . 5 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Potential candidate genes in this region include Smad 4 , Smad 2 , and Dcc . ^^^ Previously , we excluded Smad 4 and Smad 2 as candidates for Par 2 based on the lack of functional polymorphism ( s ) and differential expression in lungs from A / J and BALB / c mice . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
A competitive RT PCR system was developed to compare the levels of expression of TGFbeta 1 , TGFbeta1R 1 and TGFbeta1R 2 , Smad 2 and Smad 4 genes in all tumors . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
METHODS : Thirty nine polyps and five carcinomas from 17 patients ( from 13 families ) with PJS were analysed for loss of heterozygosity ( LOH ) at 19p13 . 3 ( STK11 / LKB1 gene locus ) , 5q21 ( APC gene locus ) , 18q21 22 ( Smad 4 and Smad 2 gene locus ) , and 17p13 ( p 53 gene locus ) , and evaluated for immunohistochemical staining of p 53 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Formation of a stable heterodimer between Smad 2 and Smad 4 . ^^^ Upon phosphorylation by the activated receptor kinases , the receptor regulated Smad , such as Smad 2 , forms a heterocomplex with the co mediator Smad , Smad 4 . ^^^ Using purified recombinant proteins , we demonstrate that Smad 2 and Smad 4 form a stable heterodimer and that the Smad 4 activation domain is important for the formation of this complex . ^^^ Mapping these mutations onto the structures of Smad 4 and Smad 2 identifies a symmetric interface between these two Smad proteins . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
While TRAP 1 has only a small stimulatory effect on TGF beta signaling in functional assays , deletion constructs of TRAP 1 inhibit TGF beta signaling and diminish the interaction of Smad 4 with Smad 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
To elucidate involvement of the transforming growth factor beta ( TGF beta ) signaling pathway in endogenous and exogenous liver carcinogenesis , we investigated mutations of TGF beta receptor type 2 ( TGF betaRII ) , Smad 2 and Smad 4 genes , and expression of TGF betaRII in hepatocellular carcinomas ( HCCs ) induced by a choline deficient L amino acid defined ( CDAA ) diet and by N nitrosodiethylamine ( DEN ) . ^^^ Total RNAs were extracted from individual HCCs and mutations in TGF betaRII , Smad 2 and Smad 4 were investigated by reverse transcription ( RT ) polymerase chain reaction ( PCR ) restriction single strand conformation polymorphism ( SSCP ) analysis followed by sequencing analysis . ^^^ Mutations of Smad 2 were detected in 2 out of 12 HCCs ( 16 . 7 % ) induced by the CDAA diet , a GGT to GGC transition ( Gly to Gly ) at codon 30 and a TCT to GCT ( Ser to Ala ) transversion at codon 118 , without any TGF betaRII or Smad 4 alterations . ^^^ No mutations of TGF betaRII , Smad 2 and Smad 4 were encountered in eleven HCCs induced by the exogenous carcinogen . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
After TGF beta mediated phosphorylation and association with Smad 4 , Smad 2 moves to the nucleus and activates expression of specific genes through cooperative interactions with DNA binding proteins , including members of the winged helix family of transcription factors , forkhead activin signal transducer ( FAST ) 1 and FAST 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
LOH was seen only in the Smad 2 gene but not in the Smad 4 gene . ^^^ Our results also suggest that genetic alteration of the Smad 2 gene is more responsible for endometrial carcinogenesis than that of the Smad 4 gene . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Potent tumor suppressor genes located in this region encode transforming growth factor beta ( TGF beta ) signal transducers SMAD 2 and SMAD 4 , and inactivation of either one leads to impaired TGF beta mediated cell growth / apoptosis . ^^^ Following the assignment of SMAD 7 to 18q21 , we first refined the SMAD 7 gene position within this region by genetically mapping SMAD 7 between SMAD 2 and SMAD 4 . ^^^ Among a subset of 233 DNA samples for which data were available for all four genes , SMAD 4 , SMAD 2 , and the nearby gene DCC showed high deletion rates ( 66 % , 64 % , and 59 % , respectively ) , whereas SMAD 7 was deleted in only 48 % of the tumors . ^^^ Compiled data for SMAD genes in each tumor show that the most common combination ( 26 % of all the tumors ) consists of the simultaneous deletions of SMAD 2 and SMAD 4 associated with normal diploidy or even duplication of SMAD 7 . ^^^ Since SMAD 7 normally counteracts SMAD 2 and SMAD 4 in TGF beta signaling , we hypothesize that the tumor might not benefit from simultaneous SMAD 7 inactivation , thereby exerting selective pressure to retain or even to duplicate the SMAD 7 gene . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Increased levels of TGFbeta 1 induced transcriptional activation of the P 1 promoter by overexpression of Smad 2 and / or Smad 4 is greatly reduced in the presence of Smad 2 ( 3SA ) and completely inhibited by Smad 7 , suggesting the participation of endogenous Smad2 / Smad4 complexes . ^^^ Overall , the present data demonstrate that Smad 2 and Smad 4 possibly in complex with FAST 1 or other DNA binding partners participate in the constitutive and inducible transactivation of the fur P 1 promoter . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Lefty did not induce Smad 2 or Smad 5 phosphorylation , Smad2 / Smad4 heterodimerization , or nuclear translocation of Smad 2 or Smad 4 , but activated the MAPK pathway in a time and dose dependent fashion . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
We demonstrate that the C terminal truncation prevents Smad 4 homomeric complex formation and heteromeric complex formation with activated Smad 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad 2 and ERK1 / 2 were activated in response to TGF beta ; however , TGF beta had little effect on the protein expression of Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Tob associated with Smad 2 and Smad 4 and enhanced Smad DNA binding . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Overexpression of Smad 2 reveals its concerted action with Smad 4 in regulating TGF beta mediated epidermal homeostasis . ^^^ Overexpression of Smad 2 increases endogenous Smad 4 and TGF beta 1 expression while heterozygous loss of Smad 2 reduces their expression levels , suggesting a concerted action of Smad 2 and 4 in regulating TGF beta signaling during skin development . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
This finding , together with mutagenesis data , pinpoints a functional interface between Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Immunohistochemistry staining was used to evaluate the expression level of two tumor suppressor candidates Smad 2 and Smad 4 in this region . ^^^ The irregular expression of tumor suppressor candidates Smad 2 and Smad 4 may play important role in the initiation and progression of bladder neoplasms . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Among 456 cases of human breast carcinoma assembled in tissue microarrays , the majority ( 92 % ) expressed Smad 2 , Smad2P , as well as Smad 4 , indicating their ability to proliferate within a microenvironment that contains bioactive TGF beta . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Thus , in human mesangial cells , the mechanism of decorin mediated inhibition of TGFbeta signalling may involve activation of Ca ( 2+ ) signalling , the subsequent phosphorylation of Smad 2 at a key regulatory site , and the sequestration of Smad 4 in the nucleus . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Three families of Smads have been identified : ( 1 ) receptor regulated Smad 2 and 3 ( R Smads ) ; ( 2 ) common partner Smad 4 ( Co Smad ) ; and ( 3 ) inhibitory Smad 6 and 7 ( 1 Smads , part of a negative feedback loop ) . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 . ^^^ The mutant Smad 2 protein exhibits decreased association with the receptor complex , is not phosphorylated in response to TGFbeta , fails to associate with Smad 4 and does not localize to the nucleus . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Oocytes from these early stages contain immunostaining for Smad 2 and Smad 4 , consistent with signaling by other TGF beta superfamily members . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
We found that E 7 interacts constitutively with Smad 2 , Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^ ARC 105 protein binds to Smad2 / 3 Smad 4 in response to TGF beta and is recruited to Activin / Nodal responsive promoters in chromatin in a Smad 2 dependent fashion . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Several candidate tumor suppressor genes , such as SMAD 2 , SMAD 4 , and DCC , are located in this region . ^^^ In contrast to the cis compound Apc ( delta 716 ) Smad 4 heterozygotes , the polyps in the cis compound Apc ( delta 716 ) Smad 2 heterozygotes showed no difference in the number , size , or histopathology from the polyps in the simple Apc ( delta 716 ) heterozygotes . ^^^ These results suggest that , on human chromosome 18q21 , the SMAD 4 LOH plays a more significant role , and SMAD 2 LOH is insufficient to cause malignant progression of colonic polyps . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
TGFbeta receptor mediated phosphorylation stimulates nuclear accumulation of Smad 2 by modifying its affinity for SARA and Smad 4 but not for CAN / Nup214 or Nup 153 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
The elevation of Smad 2 protein levels was because of increased half life and resulted in increased complex formation with Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Western blot analysis was performed to detect levels of c Myc , Smad 2 , Smad 4 , and phosphorylated Smad 2 in RIE and RIE Tr cells . ^^^ We found that Smad 2 , Smad 4 , and Smad 6 expression remained constant in RIE and RIE Tr cells with or without serum or TGF beta treatment . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
We previously have demonstrated by comparative genomic hybridization that 80 % of ulcerative colitis related cancers show loss of all or part of chromosome 18 , the site of at least three candidate tumor suppressor genes : DCC , SMAD 2 , and SMAD 4 . ^^^ TaqMan analysis was used to determine the relative copy number of five test genes on chromosome 18 ( PACAP on 18p and DCC , SMAD 2 , SMAD 4 , and GALNR on 18q ) . ^^^ By quantitative PCR analysis , a relative loss of copy number of SMAD 2 , SMAD 4 , and DCC were detected in 40 % , 57 % , and 53 % , respectively , of the colitis related cancers . ^^^ SMAD 2 was retained in four tumors having loss of SMAD 4 and DCC . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
The TGFb growth inhibitory pathway is altered either by mutations in the signal transduction molecules SMAD 2 and SMAD 4 in LOH positive tumours or by mutations of TGFbRII in MSI+ tumours . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
An allelic series of mutations in Smad 2 and Smad 4 identified in a genotype based screen of N ethyl N nitrosourea mutagenized mouse embryonic stem cells . ^^^ Here data are presented showing that a screen of a cryopreserved library of clonal , germ line competent , N ethyl N nitrosurea ( ENU ) mutagenized ES cells can identify a large series of allelic mutations in Smad 2 and Smad 4 , two nonselectable genes of the transforming growth factor beta superfamily of signaling molecules . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Phosphorylated Smad 2 and Smad 3 , together with Smad 4 , enter the nucleus and associate with various transcription factors . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Transfection with Smad 4 also induced alteration in cell phenotype , although this was not as pronounced as the effect of overexpression of Smad 2 . ^^^ Overexpression of the Smad 2 , Smad 3 , or Smad 4 proteins was associated with increased production of all collagen types . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
We further demonstrate that the ( delayed ) p 38 activation by TGF beta 1 is downstream of Smads and requires a functional Smad pathway , because blocking TGF beta induced p 38 activity with SB 202190 had no effect on Smad 2 phosphorylation , but blocking Smad signaling by forced expression of Smad 7 abolished TGF beta 1 induction of p 38 activation and , as shown earlier , BGN mRNA expression ; finally , re expression of Smad 4 in Smad 4 null CFPAC 1 cells restored TGF beta induced p 38 phosphorylation and , as demonstrated previously , BGN mRNA accumulation . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Within this chromosomal interval , the Smad 2 , Smad 4 , and Smad 7 genes were analyzed for the presence of a disease causing mutation in affected animals . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Following the definition of SMAD 4 deletion as a negative predictive marker for chemotherapy benefit in patients with CRC , we aimed to evaluate the clinical relevance of the deletion of other SMAD genes clustered in this region : SMAD 2 and SMAD 7 in 264 CRC biopsies from a previous clinical study . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The close proximity of Smad 2 , Smad 7 and Smad 4 to D18Mit189 / 210 provides a potential mechanism through which Odsm 1 might act . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
We found that the mutations at Lys 113 and Lys 159 did not alter the ability of Smad 4 to form a complex with Smad 2 and FAST on the Mix . 2 promoter . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Expression and localization of Smad 1 , Smad 2 and Smad 4 proteins in rat testis during postnatal development . ^^^ AIM : To study the expression and regulation of Smad 1 , Smad 2 and Smad 4 proteins ( intracellular signaling molecules of transforming growth factor b family ) in rat testis during postnatal development . ^^^ RESULTS : Smad 1 , Smad 2 and Smad 4 were present throughout testicular development . ^^^ The results of image and statistical analysis showed that generally the expression of Smad 1 , Smad 2 and Smad 4 in the testis tended to increase gradually with the growth of the rat . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In rat SMC , Smad 1 , Smad 2 , Smad 3 , Smad 4 and Smad 5 were detected by immunoprecipitation . ^^^ Using adenovirus mediated transfection method , we demonstrated that overexpression of Smad 2 or Smad 4 was associated with an increased production of TGF beta 1 induced plasminogen activator inhibitor 1 ( PAI 1 ) . ^^^ However , the most prominent expression of PAI 1 was observed upon cotransfection of both Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Nuclear translocation of Smad 2 and Smad 4 occurred equally in RIE Ras and parental RIE cells . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
The majority of Smad 4 gene mutations in human cancer are missense , nonsense , and frameshift mutations at the mad homology 2 region ( MH 2 ) , which interfere with the homo oligomer formation of Smad 4 protein and the hetero oligomer formation between Smad 4 and Smad 2 proteins , resulting in disruption of TGFbeta signaling . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^ Also , a LOH analysis of 18q21 , where the Smad 2 and Smad 4 genes are located , was performed . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ However , significantly lower Smad 2 and Smad 4 mRNA level was noted when the depth of myometrial invasion was considered ( p < 0 . 05 ) . ^^^ 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 Q13485	Pubmed	SVM Score :0.0
Loss of expression , and mutations of Smad 2 and Smad 4 in human cervical cancer . ^^^ However , not much information is available on Smad alterations in cervical cancer and so we probed , for the first time , for alterations in Smad 2 and Smad 4 genes using human cervical cancer cell lines and human cervical tissue samples . ^^^ Our results highlight an important role for Smad 2 and Smad 4 in human cervical tumors . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
We investigated expressions and localizations of TGR 1 , Smad 2 , Smad 4 , and Smad 7 by using semi quantitative RT PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber ' s method . ^^^ The down regulation of TGR 1 , Smad 2 , and Smad 4 was evident during the later steps of the promotion stage of chemical hepatocarcinogenesis . ^^^ Also immunohistochemistry revealed that the main site of TGR 1 , Smad 2 , Smad 4 , and Smad 7 expression was mainly in hepatocytes of the preneoplastic lesions of a rat liver . ^^^ Dysregulation of the downstream effectors of TGF beta such as TGR 1 , Smad 2 , Smad 4 and , Smad 7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
We conducted a high throughput analysis of the expression patterns of Smad 2 , phosphorylated ( activated ) Smad 2 ( pSmad 2 ) , and Smad 4 in more than 600 human colorectal cancer specimens assembled in tissue microarrays . ^^^ Twelve of 633 ( 1 . 9 % ; 95 % CI : 1 % 3 % ) cases failed to express Smad 2 , and 15 of 641 ( 2 . 3 % ; 95 % CI : 1 % 4 % ) cases failed to express Smad 4 . ^^^ Based on an analysis of 577 cases for which clinical outcome information was available , failure to express Smad 2 , pSmad 2 , or Smad 4 was associated with advanced stage disease , the presence of lymph node metastases , and a significantly shorter overall survival ( median survival : 35 vs 58 months ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In this study , we have shown that RD cells displayed higher expression of TbetaRI , TbetaRII , Smad 2 and Smad 4 at both the mRNA and protein levels than myoblasts . ^^^ TGF beta 1 signalling induced a rapid relocation of Smad 2 to the nucleus ; in contrast , Smad 4 remained localized to the cytoplasm unless it was coexpressed with Smad 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
TGF beta 1 induces a time dependent phosphorylation of Smad 2 and co immunoprecipitation of SMAD 2 with Smad 4 and its subsequently translocation to the nucleus . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Activin A induces phosphorylation of Smad 2 but not complex formation of Smad 2 with Smad 4 in human colon cancer cell line HT 29 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 ) . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ Inhibition of Smad 4 expression exhibited a partial effect , whereas inhibition of Smad 2 expression had no effect . ^^^ 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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
These loci harbour genes ( TGF beta receptor 2 gene at 3p , and Smad 2 and Smad 4 genes at 18q ) encoding products involved in the TGF beta 1 signalling pathway . ^^^ Moreover , mRNA levels of Smad 2 and Smad 4 genes were nearly constant throughout . ^^^ Thus , LOH at 3p and / or 18q seen during HPV mediated immortalization of human keratinocytes was not associated with resistance to TGF beta 1 mediated growth inhibition or a marked reduction in TGF beta 1 receptors and mRNA levels of Smad 2 or Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Using the immuno histochemistry , we investigate the expression and location of TGF beta R 2 , Smad 2 , Smad 4 and Smad 7 in 20 lung cancer specimens and 8 lung cancer cell lines . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Western blotting and reverse transcription polymerase chain reaction analyses indicated that , in response to gonadotropins , TGFbeta 2 , TbetaRI , Smad 2 and Smad 4 mRNA and protein levels increased , while those of Smad 6 decreased in ovarian homogenates . ^^^ In conclusion , these results show that , in a model of immature mouse exposed to a sequential gonadotropin treatment , FSH and LH increased the expression of the TGFbeta signaling system through the increase of TGFbeta 2 , TbetaRI , stimulatory Smad 2 , and common Smad 4 expression , which occurred concomitantly with a decrease of the inhibitory Smad 6 expression . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
The intracellular signaling proteins Smad 2 and Smad 4 are present in the granulosa cell cytoplasm of all follicle size classes . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Immunoprecipitation and immunocytochemistry revealed that Smad 2 , Smad 3 , and Smad 4 were functionally expressed in PSCs . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
When phospho Smad 2 and Smad 4 are present in the nucleus , LEF 1 is activated without beta catenin . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Albumin endocytosis induced Smad 2 phosphorylation and Smad 4 translocation as well as increased protein expression of the inhibitory Smad , Smad 7 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The TGF beta signal transduction pathways in HMC were studied by measuring the receptor regulated Smad proteins ( Smad 2 and 3 ) and common partner Smad proteins ( Smad 4 ) . pIgA 1 from patients with IgAN upregulated Smad activity in HMC , and the activity observed in HMC that had been preincubated with pIgA 1 was readily suppressed with optimal concentrations of captopril or losartan . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Transforming growth factor beta ( TGF beta ) superfamily members signal via complexes of activated Smads , comprising phosphorylated receptor regulated Smads , such as Smad 2 and Smad 3 , and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Expression of Smad 2 and Smad 4 , transforming growth factor beta signal transducers in rat endometrium during the estrous cycle , pre , and peri implantation . ^^^ To decipher the mechanism of TGF beta signaling during the estrous cycle and implantation , we performed in situ hybridization to investigate the expression patterns of mRNAs for Smad 2 and Smad 4 in rat endometrium during the estrous cycle and on Days 0 . 5 , 1 . 5 , 2 . 5 , 3 . 5 , 4 . 5 , 5 . 5 , and 6 . 5 of pregnancy . ^^^ Intense epithelial expression of Smad 2 mRNA at diestrus and proestrus was reduced at estrus and metaestrus , while Smad 4 maintained its constitutive expression during the estrous cycle . ^^^ Contrary to the dramatic Smad 4 expression , Smad 2 was highly down regulated on Day 2 . 5 and was increased on Day 3 . 5 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Expression of Smad 2 and Smad 4 in mouse uterus during the oestrous cycle and early pregnancy . ^^^ SMAD 2 and SMAD 4 are intracellular transducers of TGF beta superfamily . ^^^ In situ hybridization and semi quantitative RT PCR were employed to determine the temporal and spatial expression of Smad 2 and Smad 4 mRNA in mouse uterus during the oestrous cycle and early pregnancy . ^^^ Smad 2 mRNA was predominantly present in the luminal and glandular epithelium at dioestrus and prooestrus , while Smad 4 expression was at a steady level in the luminal and glandular epithelium throughout the oestrous cycle . ^^^ During pre implantation period , Smad 2 hybridization signals were accumulated in the luminal and glandular epithelium at a basal level ; Smad 4 mRNA appeared in the epithelium with a little variation in hybridization signal intensity . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
By RT PCR , transfection assays and immunohistochemistry , we show that ( 1 ) both MUC 4 mRNA and apomucin expression are upregulated by TGF beta , ( 2 ) Smad 2 positively cooperates with Smad 4 to activate the promoter , ( 3 ) activation of Smad 4 by exogenous TGF beta induces Smad 4 binding to the promoter , ( 4 ) Smad 7 and c ski both inhibit activation by Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Smad DNA binding activity was relatively more in SiHa than in HeLa cells upon TGF beta treatment , and the active complex contained Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^ Decreased level of SMAD 2 and SMAD 4 mRNAs was observed in the uterine tumors infiltrating less and more than half of the myometrial wall ( P = 0 . 03 and P = 0 . 02 , respectively ) compared with noninfiltrating ECs . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^ Here we investigate this nucleocytoplasmic shuttling in detail in living cells using fusions of Smad 2 and Smad 4 with enhanced GFP . ^^^ We go on to demonstrate directly , using photobleaching experiments , that Smad 2 and Smad 4 shuttle between the cytoplasm and nucleus in both TGF beta induced cells and in uninduced cells . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Here we show that loss of Itch E 3 ligase in mouse embryonic fibroblasts ( MEFs ) results in reduced susceptibility of TGF beta induced cell growth arrest and decreased phosphorylation of Smad 2 , without apparent alteration in protein levels for Smad 2 , Smad 4 , and Smad 7 in Itch / MEFs . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ CONCLUSIONS : Smad 2 , Smad 3 and Smad 4 are present and activated by TGF beta 1 in MDPC 23 cells . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Furthermore , the potentiating action of CTGF was neither dependent on modulation of TGFbeta 1 induced Smad 2 phosphorylation and its association with Smad 4 , nor did it result from nuclear accumulation of activated Smad 2 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
RESULTS : 1 ) HG up regulated the expression of Smad 2 on both gene and protein levels , especially in 2 . 5 % and 4 . 25 % dextrose groups ( P < 0 . 05 ) , and also stimulated the expression of Smad 4 in 4 . 25 % dextrose group . ^^^ CONCLUSION : A high glucose solution up regulated the expression of Smad 2 and Smad 4 , suggesting that the TGF beta 1 Smad pathway could be involved in the fibrosis of the peritoneum during PD . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Inhibition of clathrin mediated internalization only slightly affects TGF beta 1 stimulated association between SARA and Smad 2 , Smad 2 phosphorylation , or Smad 2 interaction with Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
ChIP assays show that TGF beta 1 stimulates p 53 , Smad 4 , P Smad 2 binding , and histone H3K9 deacetylation and methylation , at the SBE / p53RE . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Most human colorectal cancers are resistant to the tumor suppressor effects of TGF beta , and a subset of human colorectal cancers have mutations in Smad 2 and Smad 4 . ^^^ 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 Q13485	Pubmed	SVM Score :0.0
Previous studies have shown that altered expression of TGF beta receptors , Smad 2 and Smad 4 , as mediators of TGF beta superfamily signaling , contributes to tumor progression in esophageal squamous cell carcinoma ( SCC ) . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
We describe an equivalent mechanism of degradation of Smad 4 by the above E 3 ligases , via formation of ternary complexes between Smad 4 and Smurfs , mediated by R Smads ( Smad 2 ) or 1 Smads ( Smad6 / 7 ) , acting as adaptors . ^^^ Smad 2 or Smad 7 mutants defective in Smad 4 interaction failed to induce Smurf 1 mediated down regulation of Smad 4 . ^^^ A Smad 4 mutant defective in Smad 2 or Smad 7 interaction could not be effectively down regulated by Smurf 1 . ^^^
Interacting proteins: Q15796 and Q13485	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 . ^^^ We examined the expression of TGF beta signaling proteins Smad 2 , Smad 2 P , and Smad 4 by immunohistochemistry in 27 HPV 16 negative and 16 HPV 16 positive HNSCCs . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
METHODS AND RESULTS : Systemic infusion of Ang 2 into Wistar rats increased aortic Smad 2 , phosphorylated Smad 2 , and Smad 4 expression , associated with CTGF upregulation . ^^^ In growth arrested vascular smooth muscle cells , Ang 2 treatment for 20 minutes caused Smad 2 phosphorylation , nuclear translocation of phosphorylated Smad 2 and Smad 4 , and increased Smad DNA binding activity . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Furthermore , cells on AM continuously retained Smad 2 and Smad 4 in the cytoplasm and did not express alpha smooth muscle actin , even when 10 ng / ml TGF beta 1 was added in a serum free medium for up to 5 days . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
We found that all signal transducer Smads ( Smad 2 , 3 ; Smad 4 ) and at least one of the inhibitory Smads ( Smad 6 , 7 ) were expressed in non treated lymphoma cells , but the inhibitory Smads did not in normal / control PBMCs . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Effects on transforming growth factor beta 1 ( TGF beta 1 ) receptor binding were analyzed by flow cytometry and on TGF beta 1 signal transduction by immunoblot analyses for Smad 4 and 7 , translocation from cytosol to nucleus for Smad 2 and 3 as well as for phosphorylated and unphosphorylated forms of p 38 , c Jun NH 2 terminal kinase ( JNK ) and extracellular regulated protein kinase ( ERK ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Treatment with CM ( Cerebellum ) caused nuclear translocation of SMAD 2 and SMAD 4 , and also transactivated a TGFbeta 2 responsive gene . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
The relationship between its supposed negative prognostic influence and the inactivation of candidate tumor suppressors deleted in colorectal cancer , Smad 2 and Smad 4 has not been definitively established . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
HOXA 13 and HOXD 13 also bind to other BMP and TGF beta / Activin regulated Smad proteins including Smad 1 and Smad 2 , but not Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Involvement of SMAD 4 , but not of SMAD 2 , in transforming growth factor beta 1 induced trophoblast expression of matrix metalloproteinase 2 . ^^^ In the present study , we examined the possible role of Smad 4 and Smad 2 in transforming growth factor ( TGF ) beta 1 induced MMP 2 expression , using the well established invasive extravillous trophoblast cell line HTR 8 / SVneo . ^^^ Recombinant sense Smad 4 or Smad 2 retroviral vectors were constructed by inserting full length Smad 4 or Smad 2 cDNA into pLXSN retroviral vector . ^^^ Effects of retroviral expression of Smad 4 and Smad 2 on TGF beta 1 regulated MMP 2 expression were assessed by semi quantitative reverse transcription polymerase chain reaction and gelatin zymography . ^^^ These findings suggest that Smad 4 , but not Smad 2 , mediates TGF beta 1 induced MMP 2 expression in invasive extravillous trophoblasts . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Furthermore , activation of the Smad signaling cascade by NO is corroborated by the NO dependent increase in nuclear Smad 4 level and is paralleled by increased DNA binding of Smad 2 / 3 containing complexes to a TIMP 1 specific Smad binding element ( SBE ) . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Using fluorescence perturbation experiments on Smad 2 and Smad 4 fused to either enhanced green fluorescent protein or photoactivatable green fluorescent protein , we have studied the kinetics of Smad nucleocytoplasmic shuttling in a quantitative manner in vivo . ^^^ We find that TGF beta induced nuclear accumulation of Smad 2 is caused by a pronounced drop in the export rate of Smad 2 from the nucleus , which is associated with a strong decrease in nuclear mobility of Smad 2 and Smad 4 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The expression levels of Smad 2 , Smad 3 and Smad 4 proteins were determined by immunoblotting . ^^^ However , neither Smad 2 nor Smad 4 caused significant effects in COL1A2 promoter activity in normal fibroblasts or SSc fibroblasts . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Sham transfected and Smad 4 expressing BxPC 3 cells exhibited similar responses to TGF beta 1 with respect to p 21 upregulation , hypophosphorylation of the RB protein , Smad 2 phosphorylation , and Smad2 / 3 nuclear translocation . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	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 Q13485	Pubmed	SVM Score :0.0
Altered levels of Smad 2 and Smad 4 are associated with human prostate carcinogenesis . ^^^ We used immunohistochemistry to analyze phosphorylated Smad 2 ( p Smad 2 ) , nuclear Smad 4 and inhibitory Smad 7 in epithelial cells of normal , hyperplastic and malignant prostate . ^^^ Nuclear p Smad 2 ( P < 0 . 001 ) and nuclear Smad 4 ( P=0 . 023 ) were significantly decreased in PC with remarkable variations in cytoplasmic Smad 7 levels . ^^^ Substantial decreases in p Smad 2 and Smad 4 levels were found in specimens with primary Gleason grades 3 and 4 , whereas in grade 5 , levels were markedly higher . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
AIM : To investigate the location alteration of Smad 2 and Smad 4 mRNAs in the liver during and after fibrogenesis in rats . ^^^ In situ hybridization ( ISH ) was used to detect the Smad 2 and Smad 4 mRNA in liver . ^^^ RESULTS : In situ hybridization showed Smad 2 and Smad 4 mRNA expressions in the cytoplasm of hepatic stellate cells ( HSC ) , fibroblasts and myofibroblasts around the central vein and hepatic sinus during and after fibrogenesis . ^^^ CONCLUSION : In the process of and after hepatic fibrosis formation , HSC , fibroblasts and myofibroblasts are the major cells that express Smad 2 and Smad 4 . ^^^ The more serious the hepatic fibrosis is in the injured liver , the higher the level of Smad 2 and Smad 4 gene expression is during and after fibrogenesis respectively . . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
TGF beta signaling was monitored by measuring the promoter activity of TGF beta 1 , beta 2 , and beta RII after transient adenoviral transfection , and cytolocalization of Smad 2 and Smad 4 . ^^^ The nuclear accumulation of Smad 2 and Smad 4 and the promoter activities of TGF beta 1 and beta RII were significantly downregulated in KSFM compared with DMEM / 10 % FBS . ^^^ In KSFM , an increase of [ Ca2+ ] to 1 . 8 mM and addition of 10 % FBS synergistically downregulated the keratocan promoter activity , facilitated Smad 2 and Smad 4 nuclear translocation , and upregulated TGF beta 1 and beta RII promoter activities . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
In this work , we report that TGF beta dependent signaling is regulated by electrical activity in developing rat primary myotubes , as determined by Smad 2 phosphorylation , Smad 4 nuclear translocation , and p3TPLux reporter activity . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 Q13485	Pubmed	SVM Score :0.0
For SNU 16 , changes in ActRIA , ActRIB , ActRIIA , ActRIIB , Smad 2 , Smad 4 , Smad 7 , and p 21 ( CIP1 / WAF1 ) mRNAs were detected with RT PCR after the cells were cultured with activin A for 24 , 48 and 72 h . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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 Q13485	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 Q13485	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 Q13485	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 . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Smads are intracellular transducers for TGF beta superfamily ligands , but little is known about the mechanism by which complexes of receptor phosphorylated Smad 2 and Smad 4 regulate transcription . ^^^
Interacting proteins: Q15796 and Q13485	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 Q13485	Pubmed	SVM Score :0.0
Analysis of human meningiomas for aberrations of the MADH 2 , MADH 4 , APM 1 and DCC tumor suppressor genes on the long arm of chromosome 18 . ^^^ In the present study , we have investigated a series of 37 meningiomas for mutation and expression of 4 tumor suppressor genes ( MADH 2 , MADH 4 , APM 1 and DCC ) located at 18q21 . ^^^ None of the tumors showed mutations of MADH 2 and MADH 4 or loss of detectable transcripts from MADH 2 , MADH 4 , APM 1 and DCC . ^^^ Taken together , our data do not support a significant role for MADH 2 , MADH 4 , APM 1 and DCC alterations in the pathogenesis of meningiomas . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Exclusion of Madh 2 , Madh 4 , and Madh 7 as candidates for the modifier of Min 2 ( Mom 2 ) locus . ^^^ Residing in this region are the Madh 2 and Madh 4 genes , which have both been implicated in human colorectal cancer . ^^^ Based on meiotic recombinations within the Mom 2 region in the derivation of our congenic animals , we have narrowed the location of the Mom 2 locus and excluded Madh 2 , Madh 4 , and Madh 7 , as well as Mbd 1 , Mbd 2 , Dcc , and Tcf 4 , as candidates for the Mom 2 gene . . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The gene for MADR 2 was found to reside on chromosome 18q21 , near DPC 4 , another MADR protein implicated in pancreatic cancer . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Here , we demonstrate that MADR 2 and not the related protein DPC 4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C terminal serines . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
This region contains the putative tumor suppressor gene DCC and two Mad ( Mothers against dpp ) related genes , DPC 4 and MADR 2 , which are both components in a transforming growth factor beta like signaling pathway . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
More recent evidence suggests that other tumor suppressor genes DPC 4 and MADR 2 of the transforming growth factor beta ( TGF beta ) pathway also may be inactivated by allelic loss on chromosome 18q . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
One of the loci for neuroblastoma suppressor genes is chromosome 18q21 where the DPC 4 tumor suppressor gene , as well as the DCC and MADR 2 genes , is located . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Several candidate tumor suppressor genes have been mapped to this chromosomal region , including DCC , DPC 4 , and MADR 2 . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
Somatic alterations of the DPC 4 and Madr 2 genes in colorectal cancers and relationship to metastasis . ^^^ The DPC 4 and Madr 2 genes are located at 18q21 , and the LOH on chromosome 18q21 has been shown to occur frequently in colorectal cancers . ^^^ To investigate the role of these genes in advanced colorectal cancers , we analyzed 29 colorectal specimens for alterations in the DPC 4 and Madr 2 genes . ^^^ An alteration of the DPC 4 gene sequence was identified in 6 ( 20 . 7 % ) of 29 colorectal carcinomas , and the distinct Madr 2 gene mobility shifts were present in 3 ( 10 . 3 % ) cancers . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
The LOH frequencies were high ( > 35 % ) but were not associated with the tumor stage and progression in 20 loci , including the regions where TP 53 , E cadherin , deleted in colorectal carcinoma ( DCC ) , phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) , mothers against decapentaplegic , Drosophila , homolog of 2 ( MADH 2 ) and mothers against decapentaplegic , Drosophila , homolog of 4 ( MADH 4 ) reside . ^^^
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
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Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15796 and Q13485	Pubmed	SVM Score :0.0
NA