Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.76159277
The same three sites , which all lie in the canonical PKB consensus sequences ( Arg Xaa Arg Xaa Xaa ( Ser / Thr ) ) , became phosphorylated when FKHR was cotransfected with either PKB or PDK 1 ( an upstream activator of PKB ) . 0.76159277^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.82090028
The selective substrate specificity is correlated with an enhanced association between Akt or SGK and their preferred substrates , FKHR and B Raf , respectively . 0.82090028^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The transcription factor , forkhead in rhabdomyosarcoma ( FKHR ) , is phosphorylated at three amino acid residues ( Thr 24 , Ser 256 and Ser 319 ) by protein kinase B ( PKB ) alpha . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
HNF 3 ( hepatic nuclear factor 3 ) , FKHR ( forkhead in rhabdomyosarcoma ) ] in vitro , while insulin promotes the phosphorylation and inactivation of FKHR in a phosphatidylinositol 3 kinase and protein kinase B ( PKB ) dependent manner . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
However , insulin induced phosphorylation and regulation of protein kinase B , glycogen synthase kinase 3 and FKHR ( forkhead in rhabdomyosarcoma ) are not affected by H ( 2 ) O ( 2 ) in the same cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Recent findings demonstrate that the transcription factors FKHR ( forkhead in rhabdomyosarcoma ) , AFX ( ALL 1 fused gene from chromosome 10 ) and FKHRL 1 ( FKHR like 1 ; termed FKHR isoforms ) are phosphorylated by PKB in cells , leading to their exit from the nucleus . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Abbreviations used : FKHR , forkhead in rhabdomyosarcoma ; G6Pase , glucose 6 phosphatase ; PKB , protein kinase B ; PI 3 kinase , phosphatidyl inositol 3 kinase ; IRU , insulin responsive unit ; Tx , 4 hydroxytamoxifen , ER , estrogen receptor ; HBD , hormone binding domain . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Since Akt is known to regulate gene expression through inactivation of the transcription factor FKHR ( forkhead in rhabdomyosarcoma ) , we examined the effect of FKHR on STAT 3 mediated transcriptional regulation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The AFX ( acute lymphocytic leukaemia 1 fused gene from chromosome 10 ) , FKHR ( Forkhead in rhabdomyosarcoma ) and FKHR L 1 ( FKHR like 1 ) transcription factors are directly phosphorylated by protein kinase B , resulting in nuclear export and inhibition of transcription . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Survival signals can be elicited by the activation of phosphatidylinositol 3 kinase ( PI3K ) and Akt , both of which are known to be potent regulators of apoptosis , and Akt in turn inactivates Forkhead transcription factors , including FKHR ( Forkhead in rhabdomyosarcoma ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
There was also suppression in phosphorylated PKB Thr ( 308 ) , forkhead in rhabdomyosarcoma , S6K1 , S 6 , 4E BP 1 , and signal transducers and activators of transcription 3 Tyr ( 705 ) and Ser ( 727 ) protein levels with ILK inhibition by QLT 0254 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Various studies have implicated phosphatidylinositol 3 kinase , protein kinase B ( Akt ) , phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1 ( Foxo 1 ) / Foxo3 , and the mammalian target of rapamycin ( mTOR ) in insulin ' s effect . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Immunoperoxidase procedure ( avidin biotin complex method ) was done on paraffin embedded sections with anti phosphorylated AKT ( Thr 308 ) , anti phosphorylated p44 / 42 extracellular signal regulated kinase 1 and 2 ( ERK1 / 2 ) ( Thr202 / Tyr204 ) , anti phosphorylated forkhead in rhabdomyosarcoma ( FKHR ) ( Ser 256 ) , and anti Ki 67 antibodies . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The effect of H2O2 on downstream Akt targets was examined by Western blot using antibody against phosphorylated forkhead in rhabdomyosarcoma ( FKHR ) and phosphorylated glycogen synthase kinase ( GSK ) 3beta . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FKHR proteins contain potential sites for phosphorylation by the serine / threonine kinase Akt . ^^^ Because Akt is phosphorylated in response to insulin and has been implicated in a variety of insulin effects , we investigated whether insulin affects phosphorylation of FKHR . ^^^ Mutation of serine 253 , located in a consensus Akt phosphorylation site at the carboxyl terminal end of the forkhead domain , abolished the effect of insulin on FKHR phosphorylation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Negative regulation of the forkhead transcription factor FKHR by Akt . ^^^ Recently , a homolog of FKHR in the nematode Caenorhabditis elegans was identified called DAF 16 , which is a downstream target of two Akt homologs in an insulin related signaling pathway . ^^^ We have examined the possible role of Akt in the regulation of FKHR . ^^^ Expression of active but not inactive Akt can suppress FKHR mediated transcriptional activation . ^^^ Akt can phosphorylate FKHR in vitro on three phosphoacceptor sites , at least a subset of which can also be phosphorylated by Akt in vivo . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FKHR , a human homologue of daf 16 , contains three PKB sites and is expressed in the liver . ^^^ Insulin disrupts IRS dependent transactivation by FKHR , and phosphorylation of Ser 256 by PKB is necessary and sufficient to mediate this effect . ^^^ Antisense studies indicate that FKHR contributes to basal promoter function and is required to mediate effects of insulin and PKB on promoter activity via an IRS . ^^^ To our knowledge , these results provide the first report that FKHR stimulates promoter activity through an IRS and that phosphorylation of FKHR by PKB mediates effects of insulin on gene expression . ^^^ Signaling to FKHR related forkhead proteins via PKB may provide an evolutionarily conserved mechanism by which insulin and related factors regulate gene expression . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Protein kinase B / Akt mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR 1 . ^^^ Protein kinase B ( PKB ) / Akt , a key mediator of PI 3 kinase signal transduction , phosphorylated recombinant FKHR 1 in vitro at threonine 24 and serine 253 . ^^^ Mutants FKHR 1 ( T24A ) , FKHR 1 ( S253A ) , and FKHR 1 ( T24A / S253A ) were resistant to both PKB / Akt mediated phosphorylation and PI 3 kinase stimulated nuclear export . ^^^ These results indicate that phosphorylation by PKB / Akt negatively regulates FKHR 1 by promoting export from the nucleus . . ^^^ Protein kinase B / Akt mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Regulation of the forkhead transcription factor FKHR , but not the PAX 3 FKHR fusion protein , by the serine / threonine kinase Akt . ^^^ Here we show that Akt , but not inactive Akt , represses the transcriptional activity of FKHR , another member of the forkhead family . ^^^ FKHR mutants with alanine substitutions at three Akt phosphorylation consensus sites ( T 24 , S 256 and S 319 ) were inhibited by Akt , but mutation of all three sites rendered FKHR resistant to suppression . ^^^ By contrast , the transcriptional activity of the oncogenic PAX 3 FKHR fusion protein , containing two consensus phosphorylation sites , was not inhibited by Akt . ^^^ Importantly , Akt inhibited the translocation of FKHR to the nucleus , providing a mechanism by which Akt might regulate the transcriptional activity of FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The transcription factor FKHR is inhibited by phosphorylation in response to insulin and IGF 1 through Akt kinase . ^^^ Here we show that FKHR phosphorylation in hepatocytes conforms to a hierarchical pattern in which phosphorylation of the Akt site at S ( 253 ) , in the forkhead DNA binding domain , is a prerequisite for the phosphorylation of two additional potential Akt sites , T ( 24 ) and S ( 316 ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The FKHR 208 652 fragment contains two consensus sites for phosphorylation by protein kinase B ( PKB ) / Akt , Ser 253 and Ser 316 . ^^^ Neither site is required for insulin inhibition of promoter activity stimulated by the FKHR fragment , and overexpression of Akt does not inhibit FKHR fragment stimulated Gal 4 promoter activity . ^^^ Phosphorylation of this site also may be involved in insulin inhibition of transcription activation by full length FKHR , but only after phosphorylation of Ser 253 by PKB / Akt . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Mammalian DAF 16 homologues include AFX , FKHR and FKHRL 1 , which contain a conserved forkhead domain and three putative phosphorylation sites for the Ser / Thr kinase Akt / protein kinase B ( PKB ) , as well as for DAF 16 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Coexpression of the Forkhead transcription factor FKHR stimulates the glucose 6 phosphatase promoter activity via interaction with an insulin response unit ( IRU ) , and this activation is suppressed by protein kinase B . ^^^ Coexpression of a mutated form of FKHR that can not be phosphorylated by protein kinase B abolishes the regulation of the glucose 6 phosphatase promoter by protein kinase B and disrupts the ability of insulin to regulate the glucose 6 phosphatase promoter via the IRU . ^^^ Mutation of the insulin response unit of the glucose 6 phosphatase promoter also prevents the regulation of promoter activity by FKHR and protein kinase B but only partially impairs the ability of insulin to suppress both basal and dexamethasone / cAMP stimulated promoter function . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
After establishing ErbB 1 , cbl , PI 3 kinase and Akt were activated in EGF treated MDA MB 231 , we determined by immunoblot with FKHR antiserum that the electrophoretic mobility of FKHR was retarded after EGF treatment . ^^^ This mobility retardation was reversible by treatment with alkaline phosphatase , and immunoblot with phospho Ser 256 FKHR antibody further confirmed phosphorylation on an Akt consensus site after EGF treatment . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Here we show that Forkhead transcription factors FKHRL 1 and FKHR , substrates of the Akt kinase , are aberrantly localized to the cytoplasm and can not activate transcription in PTEN deficient cells . ^^^ Expression of a constitutively active form of FKHR that can not be phosphorylated by Akt produces the same effect as reconstitution of PTEN on PTEN deficient tumor cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We show that in mammalian cells , C . elegans DAF 16 is a direct target of AKT and that AKT phosphorylation generates 14 3 3 binding sites and regulates the nuclear / cytoplasmic distribution of DAF 16 as previously shown for its mammalian homologs FKHR and FKHRL 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Furthermore , coexpression of Akt DD with MTY315 / 322F resulted in phosphorylation of the FKHR forkhead transcription factor and translational upregulation of cyclin D 1 levels . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
These signals trigger the protein kinase B ( PKB ) catalysed phosphorylation of FKHR at three residues ( Thr ( 24 ) , Ser ( 256 ) and Ser ( 319 ) ) by a phosphoinositide 3 kinase dependent pathway that results in the nuclear exit and inactivation of this transcription factor . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In addition , GSK 3 inhibition does not result in the subsequent activation of protein kinase B or inhibition of the transcription factor FKHR , which are candidate regulatory molecules for these promoters . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
On the contrary , the significant decrease of Shc phosphorylation , Grb 2 recruitment and the reduced phosphorylation level of Akt Thr 308 and Akt substrates FKHR and Bad detected in transgenic glands show that activation of the Shc and the Akt pathways require intact cell ECM interactions . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Expression of T / S / S , in which three putative protein kinase B ( PKB ) sites in FKHR are mutated , reduced insulin inhibition of basal expression of IGFBP 1 but not PEPCK . ^^^ Mutation of the PEPCK IRS had no effect on insulin inhibition in the presence of T / S / S , indicating that insulin inhibits PEPCK transcription independently of the IRS or of the putative PKB phosphorylation sites in FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
It is shown here that engagement of CCR 9 with TECK leads to phosphorylation of Akt ( protein kinase B ) , mitogen activated protein kinases ( MAPKs ) , glycogen synthase kinase 3 beta ( GSK 3 beta ) , and a forkhead transcription factor , FKHR , in a human T cell line , MOLT 4 , that naturally expresses CCR 9 . ^^^ Akt , GSK 3 beta , FKHR , and MAPK have been previously implicated in cell survival signals in response to an array of death stimuli . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Insulin regulation of gene expression through the forkhead transcription factor Foxo 1 ( Fkhr ) requires kinases distinct from Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
IL 6 also induced phosphorylation of downstream targets of Akt , including Bad , GSK 3beta , and FKHR , confirming Akt activation . ^^^ Finally , we show that IL 6 triggered PI 3 K / Akt signaling in MM . 1S cells inactivates forkhead transcriptional factor ( FKHR ) , with related G1 / S phase transition , whereas LY 294002 blocks this signaling , resulting in upregulation of p 27 ( KIP 1 ) and G 1 growth arrest . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In most cells , three serine / threonine moieties in FKHR family members are phosphorylated after insulin treatment or protein kinase B / Akt ( PKB ) transfection , and each of the three phosphorylated PKB sites contributes to insulin or PKB mediated inhibition of both the action and the nuclear localization of FKHR family members . ^^^ In hepatocytes , however , the middle PKB site ( PKB 2 ) of FKHR was required for insulin to phosphorylate FKHR and was the only PKB site that participated in insulin inhibition of FKHR action , indicating that insulin utilizes a unique pathway to regulate FKHR action in hepatocytes . ^^^ All FKHR forms stimulated IGFBP 1 promoter activity , and mutating any of the three FKHR PKB sites impaired the ability of insulin both to inhibit FKHR stimulated IGFBP 1 promoter activity and to induce FKHR accumulation in cytoplasm . ^^^ Thus , in hepatocytes as in other cell lines , all three FKHR PKB sites participate in insulin mediated inhibition of FKHR action and in insulin mediated accumulation of FKHR in cytoplasm . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FKHR , FKRHL 1 , and AFX may similarly be the major outputs of mammalian insulin signaling . daf 2 insulin signaling , via AKT kinases , negatively regulates DAF 16 by controlling its nuclear localization . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The signaling pathway that mediates these events requires the activation of phosphatidylinositol 3 kinase , whereas transfection studies have suggested an involvement of Akt ( protein kinase B ) and FKHR , a transcription factor regulated by Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
ICAM 2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation , resulting in phosphatidylinositol 3 , 4 , 5 production , PDK 1 and AKT activation , and subsequent phosphorylation of AKT targets BAD , GSK 3 , and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Basal phosphorylation of IRS 1 , PKB and ERK were unaffected whereas basal phosphorylation of CREB and FKHR were significantly increased ( 37 and 33 % , respectively ) with aging . desIGF 1 caused a significant decrease in plasma glucose concentrations in both young ( 53 % ) and old ( 44 % ) mice . desIGF 1 administration significantly increased the phosphorylation of IRS 1 in both young ( 104 % ) and old ( 89 % ) hepatic tissues . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
However , the effects of FSH and IGF 1 differ markedly in differentiated granulosa cells in which FSH ( but not IGF 1 ) induces Sgk and enhances phosphorylation of FKHR , PKB , and Sgk . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The FOXO family of Forkhead transcription factors , FKHR ( FOXO 1 ) , FKHR L 1 ( FOXO3a ) and AFX ( FOXO 4 ) , are regulated by the phosphoinositide 3 kinase protein kinase B ( PI3K PKB / c Akt ) pathway . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In the current study , they demonstrated that the activation of FKHR , a Forkhead transcription factor and a substrate for Akt , preceded delayed neuronal death in CA 1 regions after transient forebrain ischemia . ^^^ The dephosphorylation of FKHR was correlated with the decreased Akt activity . ^^^ These results suggest that the inactivation of Akt results in the activation of FKHR and , in turn , relates to the expression of Fas ligand in the CA 1 region after transient forebrain ischemia . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FKHR contains three predicted protein kinase B phosphorylation sites ( Thr 24 , Ser 256 , and Ser 319 ) that are conserved in other FOXO proteins . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
L1 ) , and FoxO1a ( FKHR ) represent important physiological targets of phosphatidylinositol 3 kinase ( PI3K ) / protein kinase B ( PKB ) signaling . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Activation of Akt maintains Bad phosphorylation and prevents its binding to mitochondrial targets , decreases caspase 9 activity , and prevents the translocation of forkhead transcription factors ( FKHR ) . ^^^ Akt , Bad , FKHR phosphorylation , and mitochondrial cytochrome release were analyzed by Western blots . ^^^ Akt activation ; increase in islet viability ; and decrease in Bad phosphorylation , cytochrome release , caspase 9 activation , and translocation of FKHR were observed after simvastatin treatment , effects reversed by LY 294002 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
AKT independent protection of prostate cancer cells from apoptosis mediated through complex formation between the androgen receptor and FKHR . ^^^ Recent studies suggested that the protection of cell apoptosis by AKT involves phosphorylation and inhibition of FKHR and related FOXO forkhead transcription factors and that androgens provide an AKT independent cell survival signal in prostate cancer cells . ^^^ Transcriptional analysis demonstrated that activation of the androgen receptor caused an inhibition of both wild type FKHR and a mutant in which all three known AKT sites were mutated to alanines , showing that the repression is AKT independent . ^^^ These studies identify a new mechanism for androgen mediated prostate cancer cell survival that appears to be independent of the activity of the receptor on androgen response element mediated transcription and establish FKHR and related FOXO forkhead proteins as important nuclear targets for both AKT dependent and independent survival signals in prostate cancer cells . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Activated Akt increased phosphorylation of downstream substrates such as GSK 3 , p 70 ( S6K ) , 4EBP 1 , and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Our data suggest that cyclic stretch activates the phosphoinositide 3 kinase ( PI3K ) pathway including : PI3K , Akt , FKHR , and AFX . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Coexpression of FKHR stimulates the PGC 1 promoter activity via interaction with the IRSs , while coexpression of FKHR ( 3A ) , in which the three putative PKB sites in FKHR are mutated , mainly abolishes the suppressive effect of PKB . ^^^ These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC 1 promoter activity via the IRSs . . ^^^ Regulation of PGC 1 promoter activity by protein kinase B and the forkhead transcription factor FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Ceramide induced neuronal apoptosis is associated with dephosphorylation of Akt , BAD , FKHR , GSK 3beta , and induction of the mitochondrial dependent intrinsic caspase pathway . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The EGFR and a number of effector kinases ( mitogen activated protein extracellular signal regulated kinase kinase 1 and 2 , MAPK , Pak 1 , p 38 , c JunNH ( 2 ) terminal kinase and extracellular signal regulated kinase 1 ) and cell survival proteins ( AKT , FKHR , and c Src ) showed constitutive pathway activation in HaCaT and cutaneous squamous cell carcinoma cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
BTC rapidly induced the phosphorylation of Akt , GSK3alpha / beta , and two FoxO factors , FKHR and AFX , in a dose and time dependent manner . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Phosphorylation of Akt and its downstream molecules [ FKHR ; Forkhead ( Drosophila ) homologue 1 ; and GSK 3beta ; glycogen synthase kinase 3 beta ] was significantly associated with pPTEN ( P < 0 . 001 ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Preventing Rap activation also increased the ability of the BCR to stimulate Akt dependent phosphorylation of the FKHR transcription factor on negative regulatory sites and decreased the levels of p27Kip1 , a pro apoptotic factor whose transcription is enhanced by FKHR . ^^^ Thus activation of endogenous Rap by the BCR limits BCR induced activation of the PI3K / Akt pathway , opposes the subsequent inhibition of the FKHR / p27Kip1 pro apoptotic module , and enhances BCR induced cell death . ^^^ Consistent with the idea that Rap GTP is a negative regulator of the PI3K / Akt pathway , expressing constitutively active Rap 2 ( Rap2V12 ) reduced BCR induced phosphorylation of Akt and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The knock in ES cells were viable , mutant PDK 1 was expressed at normal levels and insulin like growth factor 1 induced normal activation of PKB and phosphorylation of the PKB substrates GSK 3 and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Our data also demonstrate that Akt / protein kinase B , an established kinase for FKHR , is phosphorylated in response to FSH treatment . ^^^ Interestingly , although FKHR was phosphorylated by 30 min after FSH treatment , the time course for Akt phosphorylation was relatively delayed and sustained . ^^^ Although these studies do not preclude Akt involvement in FSH stimulated FKHR phosphorylation , they do suggest that other kinases may contribute to rapid signaling to FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
These studies show that the bacterial chemoattractant , formyl Met Leu Phe ( fMLP ) , promotes the phosphorylation / inactivation of the FOXO subfamily of forkhead transcription factors ( FKHR , FKHR L 1 , and AFX ) through the phosphatidylinositol 3 kinase / Akt ( protein kinase B ) and the RAS mitogen activated protein kinase pathways . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Phosphorylation of Akt , FKHR , and FKHRL 1 are phosphatidylinositol 3 kinase ( PI 3 kinase ) dependent since phosphorylation is reduced by the PI 3 kinase inhibitors , wortmannin , or LY 294002 . ^^^ CONCLUSION : We conclude that PI 3 kinase and Akt are activated after renal ischemia / reperfusion and that Akt phosphorylation leads to phosphorylation of FKHR and FKHRL 1 , which may affect epithelial cell fate in acute renal failure . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In addition , the signal to FKHR degradation from insulin is mediated by the phosphatidylinositol 3 kinase pathway , and the mutation of FKHR at the serine or threonine residues phosphorylated by protein kinase B , a downstream target of phosphatidylinositol 3 kinase , inhibits the ubiquitination in vivo and in vitro . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In particular , we found that the inhibitor blocked phosphorylation of AKT , GSK 3beta , and the pro apoptotic transcription factor FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Consistent with SH 2 Bbeta enhancing the activity of Akt , cells overexpressing SH 2 Bbeta but not SH 2 Bbeta ( R555E ) exhibited increased and / or prolonged phosphorylation of the pro apoptotic Akt effector proteins , glycogen synthase kinase 3 , and forkhead transcription factors , FKHRL1 / FOXO3 and FKHR / FOXO1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Although treatment with LY 294002 , a specific inhibitor of PI 3 K , decreased the phosphorylation of Akt and increased Fkhr translocation to the nucleus , these events were not sufficient to induce FasL expression and apoptosis of C 6 glioma cells . ^^^ Interference with Akt / Forkhead signalling by membrane targeted Akt or removal of the FKHR binding sites from the FasL promoter significantly abolished its activation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
More significantly , we have demonstrated for the first time that the phosphorylation of FKHR , a downstream target of Akt , is increased in these cell lines . ^^^ Intriguingly , phosphorylation of three components of the PI 3 kinase signaling pathway , namely Akt , p 70 S6 kinase and FKHR , are in direct correlation with the degree of tumorigenic potential of the colon cell lines tested . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
LMP2A activated Akt in a PI3K dependent manner , and the downstream Akt targets glycogen synthase kinase 3beta ( GSK3beta ) and the Forkhead transcription factor FKHR were phosphorylated and inactivated in LMP2A expressing HFK cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We further demonstrate that cav 1 stimulated Akt activities lead to increased phosphorylation of multiple Akt substrates , including GSK 3 , FKHR , and MDM 2 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Sprague Dawley adult male rats were exposed during sleep to IH or to normoxia ( RA ) for periods ranging from 0 to 30 days , and expression of total and phosphorylated AKT , of forkhead family members FKHR and FKHRL 1 , and of glycogen synthase kinase 3beta ( GSK3beta ) was assessed . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The phosphorylation of downstream molecules of Akt , forkhead transcription factors ( FKHR ) , endothelial nitric oxide synthase ( eNOS ) , and glycogen synthase kinase 3beta ( GSK 3beta ) was also increased . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The EGCG dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates , including p90RSK , FKHR , and BAD . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We here demonstrated that the activation of FKHR , a Forkhead transcription factor and a substrate for Akt , precedes the delayed neuronal death in CA 1 regions after transient forebrain ischemia . ^^^ The dephosphorylation of FKHR was correlated with the decreased Akt activity . ^^^ These results suggested that the inactivation of Akt results in the activation of FKHR and , in turn , relates to the expression of Fas ligand in the hippocampal CA 1 region after transient forebrain ischemia . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We also demonstrate that activation of Akt by the K 1 protein leads to the phosphorylation and inhibition of members of the forkhead ( FKHR ) transcription factor family , which are key regulators of cell cycle progression and apoptosis . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Inhibition of Akt increased the FKHR / Bim response and DNA fragmentation within the normally resistant cortex . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In this report , we demonstrate that Ang 1 , via Akt activation , is a potent inhibitor of the forkhead transcription factor FKHR ( FOXO 1 ) , identifying for the first time a nuclear signaling pathway through which Ang 1 modulates gene expression . ^^^ Analysis of gene expression changes induced by an activated version of Akt confirms that FKHR is a major target through which Akt regulates transcription in endothelial cells . ^^^ Our data suggest a novel , tissue specific role for the Akt / FKHR pathway in the vasculature and suggest a mechanistic basis for the previously described actions of Ang 1 as a regulator of endothelial cell survival and blood vessel stability . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
RESULTS : Concomitant with the induction of chemokine expression by the stimuli , there was phosphorylation of PI3K and its downstream targets namely , Akt , GSK , and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The phosphorylation of FKHR , FKHRL , and Bcl 2 family member Bad was markedly increased in response to oxidant injury , and this increase was associated with elevated levels of basal phosphorylation of Akt / protein kinase B . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
IGF 1 stimulation of the PI3K / Akt pathway phosphorylates three known Akt effectors : the survival transcription factor cyclic AMP response element binding protein ( CREB ) and the pro apoptotic effector proteins glycogen synthase kinase 3beta ( GSK 3beta ) and forkhead ( FKHR ) . ^^^ IGF 1 regulates survival at the nuclear level through accumulation of phospho Akt in DRG neuronal nuclei , increased CREB mediated transcription , and nuclear exclusion of FKHR . ^^^ These data suggest that IGF 1 prevents apoptosis in DRG neurons by regulating PI3K / Akt pathway effectors , including GSK 3beta , CREB , and FKHR , and by blocking caspase activation . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Furthermore , PI3K AKT appeared to regulate D type cyclin transcription in RMS lines through FKHR and FKHRL 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Restoration of SHIP expression in Jurkat cells with an inducible expression system caused a 69 % reduction of phosphatidylinositol 3 , 4 , 5 trisphosphate ( PtdIns ( 3 , 4 , 5 ) P ( 3 ) ) and a 65 % reduction of Akt kinase activity , which was associated with reduced phosphorylation of glycogen synthase kinase 3beta ( GSK 3beta ) ( Ser 9 ) without changing the phosphorylation of Bad ( Ser 136 ) , FKHR ( Ser 256 ) or MAPK ( Thr 202 / Tyr 204 ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Combined treatment also resulted in pronounced reductions in levels of phospho Akt , glycogen synthase kinase 3 ( GSK 3 ) , p 70 ( S6K ) , mammalian target of rapamycin ( mTOR ) , forkhead transcription factor ( FKHR ) , caspase 9 , and Bad . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Here we studied the forkhead ( FH ) in rhabdomyosarcoma ( FKHR ) transcription factor , which is controlled by Akt signaling and is involved in regulating cell cycle progression and cell death . ^^^ Here , for the first time , we report the contrary expression of phosphorylation of two members in the insulin like growth factor signaling pathway during hibernation ( i . e . , phosphorylated FKHR was significantly up regulated as phosphorylation of its upstream kinase , Akt , was significantly down regulated ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Furthermore , naltrindole treatment not only reduced the phosphorylation of the Akt / PKB upstream kinase phosphoinositide dependent kinase 1 , but also its downstream effectors glycogen synthase kinase 3beta and the Forkhead transcription factors AFX and FKHR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Moreover , Akt phosphorylates and thus inactivates the pro apoptotic proteins BAD and Forkhead transcription factors ( FKHR , FKHRL 1 ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The phosphorylation of two downstream targets of Akt , glycogen synthase kinase 3beta and FKHR ( forkhead transcription factor ) , was also enhanced by 2 and 2 . 9 fold , respectively . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Nicotinic activation of Akt increased phosphorylation of multiple downstream substrates of Akt in a time dependent manner , including GSK 3 , FKHR , tuberin , mTOR and S6K1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Among the many molecules involved in the intracellular processing of the signal provided by insulin , insulin receptor substrate ( IRS ) 2 , the protein kinase B ( PKB ) beta isoform and the forkhead transcription factor Foxo1a ( FKHR ) are of particular interest in this context as recent data have provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Biochemical analyses of these cells showed that mutant PIK3CA selectively regulated the phosphorylation of AKT and the forkhead transcription factors FKHR and FKHRL 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FKHR is phosphorylated on three sites ( Thr 24 , Ser 256 , and Ser 319 ) in a phosphatidylinositol 3 kinase ( PI3K ) / Akt dependent manner , thereby inhibiting death signals . ^^^ Sodium orthovanadate , a protein tyrosine phosphatase inhibitor , up regulated Akt activity in the brain and in turn rescue neurons from delayed neuronal death by inhibiting FKHR dependent or independent death signals in neurons . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Lack of Bag 1 did not disturb the primary function of Akt or Raf , as phosphorylation of the forkhead transcription factor FKHR and activation of extracellular signal regulated kinase ( Erk ) 1 / 2 were not affected . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Other Akt downstream targets , BAD , caspase 9 and the Forkhead transcription factor ( FKHR ) , were not phosphorylated during the course of infection by EV 71 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In humans , increased phosphorylation of the PKB signaling pathway related proteins Bad and forkhead transcription factor ( FKHR ) was detected in patients with TBI versus controls . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Akt kinase blocks apoptosis by phosphorylating the substrates forkhead transcription factor ( FKHR ) and glycogen synthase kinase 3beta ( GSK3beta ) . ^^^ Hypothermia may protect from ischemic damage in part by preserving Akt activity and attenuating the apoptotic effects of PTEN , PDK 1 , and FKHR . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Expression levels of PTEN , phosphorylated forms of the constituent proteins ( Akt , FKHR , mTOR , and S 6 ) and cyclin D 1 were evaluated by immunohistochemistry , on consecutive sections from a tissue microarray containing 145 invasive breast cancers and 140 pure ductal carcinomas in situ . ^^^ In all , 33 , 15 , 32 , and 60 % of ductal carcinoma in situ showed overexpression of Akt , FKHR , mTOR , and cyclin D 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
This study investigated whether estradiol modulates the anti apoptotic signal through the activation of Akt and its downstream targets , including forkhead transcription factors FKHR and FHKRL 1 . ^^^ Our findings suggest that estradiol plays a potent protective role against brain injury and that Akt activation and FKHR phosphorylation by estradiol mediated these protective effects . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Upon similar condition , nLDL inhibited the phosphorylation of Akt and two of its downstream targets , fork head receptor ( FKHR ) and glycogen synthase kinase 3 ( GSK 3 ) . ^^^ At the 4 h time point , upon a substantial decrease in nLDL induced Akt phosphorylation , scyphostatin has inhibited the reduction in FKHR and GSK 3 phosphorylation but inexplicably not that of Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Atrogin 1 and MuRF 1 , two ubiquitin E 3 ligases , mediate rodent and cell muscle atrophy and are suggested to be regulated by an Akt / Forkhead ( FKHR ) signaling pathway . ^^^ Here we investigated the expression of atrogin 1 , MuRF 1 , and the activity of Akt and its catabolic ( FKHR and FKHRL 1 ) and anabolic ( p 70 ( s6k ) and GSK 3beta ) targets in human skeletal muscle atrophy . ^^^ The transcriptional regulation of human atrogin 1 may be controlled by an Akt mediated transcription factor other than FKHR or via another signaling pathway . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Over expression of PTEN by PTEN cDNA transfection up regulates p 53 content and increases the sensitivity of chemoresistant cells to cisplatin induced apoptosis without detectable changes in the levels of phosphorylated Akt and FKHR as well as FasL mRNA abundance as determined by Western blot and RT PCR , respectively . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
METHODS : Quantitative Western blot analysis and immunocytochemistry were used to examine the activation status and localization of key components of the Akt signaling cascade ( Akt , BAD , Forkhead [ FKHR ] , HSP 27 , mitogen activated protein ( MAP ) kinase kinase 3 and 6 ( MKK3 / 6 ) , the tumor suppressor phosphatase PTEN , and the cytoplasmic protein tyrosine kinase cSrc p 60 ) , in the retina of the rd mouse in comparison with the control . ^^^ RESULTS : In the period up to the peak of photoreceptor apoptosis at postnatal day 15 , dysregulation of the survival pathway was identified at several levels , including deactivation of both Akt itself and its downstream transcription factor target Forkhead ( FKHR ) and activation of the upstream negative regulator PTEN . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Activation of PI3K by K 1 results in activation of Akt kinase and mammalian target of rapamycin and inactivation of the proapoptotic proteins FKHR , glycogen synthase kinase 3 , and Bad , which are events indicative of cell survival . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Higher activation of Akt was associated with increased phosphorylation of its downstream targets glycogen synthase kinase 3beta ( GSK3beta ) , FKHR , and mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
VLP induced PI 3 kinase activity resulted in efficient downstream signaling to Akt and consequent phosphorylation of FKHR and GSK3beta . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo 1 , a substrate of the Akt kinase that is inhibited by insulin through phosphorylation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Further analysis of pro apoptotic downstream targets of PKB , implicated a role for PKB mediated phosphorylation inhibition of glycogen synthase kinase 3alpha / beta and the forkhead transcription factor , FoxO 1 , in protection of FFA induced beta cell apoptosis . ^^^ Hence , these data demonstrate that PKB activation plays an important role in promoting pancreatic beta cell survival in part via inhibition of the pro apoptotic proteins glycogen synthase kinase 3alpha / beta , FoxO 1 , and p 53 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Expression of activated Akt triggered proteasome dependent declines in the protein levels of the Akt substrates tuberin , FOXO 1 , and FOXO3a . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In this study , we investigated the involvement of PKB , FoxO 1 , FoxO 3 , and FoxO 4 in c kit mediated survival . ^^^ RESULTS : Upon KL stimulation , PKB and its downstream target FoxO 3 , and to some extent FoxO 1 , were rapidly phosphorylated . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In keeping with its important physiological roles , Foxo 1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3 kinase ( PI 3 kinase ) protein kinase B ( PKB ) / Akt pathway . ^^^ PKB / Akt mediated phosphorylation of Foxo 1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo 1 from the nucleus , which is generally believed to explain the subsequent decrease of transcription . ^^^ Insulin inhibition of Foxo 1 ( 208 652 ) stimulated transactivation is mediated by PI 3 kinase but in contrast to full length Foxo 1 , does not require either of the two PKB / Akt phosphorylation sites ( Ser 253 and Ser 316 ) present in the protein fragment . ^^^ PKB / Akt mediated phosphorylation of Foxo 1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo 1 from the nucleus , which is generally believed to explain the subsequent decrease of transcription . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
This effect on p27Kip1 protein was associated with decreased mRNA levels as well as p27Kip1 promoter activity . 11 , 12 EET also stimulated the time dependent phosphorylation of Akt and of the forkhead factors FOXO 1 and FOXO3a , effects prevented by the phosphatidylinositol 3 kinase inhibitor LY 294002 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We also show that Akt activation is significantly correlated with phosphorylation of mammalian target of rapamycin ( mTOR ) , the family of forkhead transcription factors ( FOXO 1 , FOXO3a , and FOXO 4 ) , and S 6 , which are thought to promote its effects . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
When a mutated FoxO 1 ( without Thr 24 , Ser 256 , and Ser 316 Akt phosphorylation sites ) was used , IGF 1 was no longer able to reverse the FoxO 1 induced stimulation of p27Kip1 promoter activity that had been seen when WT FoxO 1 was present . ^^^ When the satellite cells were treated with IGF 1 , phosphorylation of Akt Ser 473 and FoxO 1 Ser256 was increased . ^^^ In addition , when the cells were pre incubated with LY 294002 before IGF 1 stimulation , the phosphorylation of Akt Ser 473 and FoxO 1 Ser256 was inhibited , implying that phosphorylation of Akt and FoxO 1 was downstream of IGF 1 induced PI3K signaling . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We show that a constitutively active Foxo 1 mutant inhibits differentiation of C2C12 cells and prevents myotube differentiation induced by constitutively active Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Several laboratories have demonstrated that Akt inhibits transcriptional activation of a number of related forkhead transcription factors now referred to as FoxO 1 , FoxO 3 , and FoxO 4 . ^^^ Here , we present our findings showing that the PI3K / Akt axis regulates cell cycle progression of HL 60 cells through multiple mechanisms also involving the control of FoxO 1 and FoxO 3 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Downstream PI 3 kinase , activation of Akt , glycogen synthase kinase ( GSK ) 3 ( alpha and beta isoforms ) , Foxo 1 , and atypical protein kinase C were blunted in insulin stimulated IRS 2 ( / ) cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Moreover , the mechanism for this inhibition involves Akt mediated inhibition of the FoxO family of transcription factors ; a mutant form of FOXO 1 , which prevents Akt phosphorylation , thereby prevents Akt mediated inhibition of MuRF 1 and MAFbx upregulation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
A constitutively active mutant of the insulin responsive protein kinase Akt , but not the kinase negative mutant , effectively blocked FOXO 1 activity in cell based assays . ^^^ Thus , insulin could repress the receptors by activating the Akt FOXO 1 signal , whereas drugs could interfere with FOXO 1 mediated transcription by activating CAR and / or PXR . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Proteasomal degradation of the FoxO 1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins . ^^^ The winged helix transcription factor FoxO 1 is a growth attenuating and proapoptotic protein and serves as a substrate of Akt . ^^^ Here we show that FoxO 1 expression is constitutively suppressed in CEF transformed by P3k or Akt . ^^^ These data suggest that phosphorylation dependent degradation of FoxO 1 by means of proteasomes plays a role in oncogenic transformation by P3k and Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
IL 7 induced PI3K dependent phosphorylation of Akt and its downstream targets GSK 3 , FOXO 1 , and FOXO3a . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Unexpectedly , they show that while the BCR induced phosphorylation of the PI3K dependent kinase Akt is reduced in p85alpha deficient cells , the phosphorylation of two downstream targets of Akt FOXO 1 and ribosomal protein S 6 is largely unaffected . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Foxo 1 , a member of the Fox 0 subfamily of winged helix forkhead transcription factors , is a target of insulin and insulin like growth factor 1 ( IGF 1 ) signal transduction pathways that activate protein kinase B ( PKB ) in pancreatic beta cells . ^^^ Foxo 1 is a substrate for PKB , and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation . ^^^ Because activation of PKB can require insulin receptor substrate proteins ( IRS 1 and IRS 2 ) and phosphatidylinositol 3 kinase ( PI3K ) , it is of interest to determine whether the activity of Foxo 1 is also regulated by heterotrimeric G protein coupled receptors ( GPCRs ) with IRS 1 or 2 , PI3K , or PKB signaling potential . ^^^ By promoting nuclear exclusion of Foxo 1 in a PKB mediated manner , GLP 1 may up regulate the expression of a homeodomain transcription factor ( PDX 1 ) that serves as a master regulator of beta cell growth and differentiation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
C2C12 cells expressing an inducible construct with either wild type FoxO 1 or a mutant form ( FoxO1 / TSS ) refractory to the protein kinase B inhibitory effects were generated . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The alterations in the dual knockdown mice were associated with defective Akt activation and Foxo 1 phosphorylation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Stable activation of phosphatidylinositol 3 kinase in the T cell immunological synapse stimulates Akt signaling to FoxO 1 nuclear exclusion and cell growth control . ^^^ This persistent activation of PI3K results in the Akt dependent sequestration of the FoxO transcription factor , FoxO 1 , outside the nucleus of T cells interacting with APCs . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Glucose dependent insulinotropic polypeptide ( GIP ) stimulation of pancreatic beta cell survival is dependent upon phosphatidylinositol 3 kinase ( PI3K ) / protein kinase B ( PKB ) signaling , inactivation of the forkhead transcription factor Foxo 1 , and down regulation of bax expression . ^^^ INS 1 cells incubated under proapoptotic and glucolipotoxic conditions demonstrated increased nuclear localization of Foxo 1 and bax promoter activity and decreased cytoplasmic phospho PKB / Foxo1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Forkhead transcription factors ( FOXO 1 , FOXO3a , FOXO 4 ) exert proapoptotic effects and are phosphorylated and , thereby , inactivated by Akt . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Specifically , GDNF induces phosphorylation of Akt and loss of the Akt substrates FOXO 1 and FOXO3a from the nucleus of ENS precursors . ^^^ Furthermore , dominant negative Akt or active FOXO 1 constructs promote ENS precursor cell death while a dominant negative FOXO 1 construct prevents cell death . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Addition of epidermal growth factor ( EGF ) ( 10 nM ) to neonatal rat cardiomyocytes caused rapid phosphorylation of Akt and slower FOXO 1 phosphorylation . ^^^ In contrast , the alpha 1 adrenergic receptor agonist phenylephrine ( 50 microM ) did not phosphorylate Akt and caused dephosphorylation of FOXO 1 acutely and increased FOXO 1 expression with chronic exposure . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The Irs 2 branch of the insulin / insulin like growth factor signaling cascade activates the phosphatidylinositol 3 kinase > Akt > Foxo 1 cascade in many tissues , including hepatocytes and pancreatic beta cells . ^^^ Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs 2 ( / ) mice and increased Akt and Foxo 1 phosphorylation in the islets . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
PGC 1alpha gene expression is down regulated by Akt mediated phosphorylation and nuclear exclusion of FoxO 1 in insulin stimulated skeletal muscle . ^^^ There are multiple binding domains on the promoter region of the peroxisome proliferator activator receptor gamma coactivator 1 alpha ( PGC 1alpha ) gene , including a trio of insulin responsive elements that are activated by the forkhead box class O ( FoxO 1 ) winged helix transcription factor , which is known to be regulated by acute transforming retrovirus thymoma ( Akt ) . ^^^ Here we show that in skeletal muscle biopsy specimens from healthy humans and cultured human skeletal myotubes , insulin phosphorylates Akt ( Ser 473 ) and FoxO 1 ( Thr 24 , Ser 256 ) , leading to reduced nuclear abundance of FoxO 1 total protein . ^^^ In contrast , in muscle taken from insulin resistant humans or in palmitate treated insulin resistant myotubes , neither Akt nor FoxO 1 was phosphorylated by insulin , resulting in a failure for nuclear exclusion of FoxO 1 total protein , and an inability for insulin to repress the mRNA expression of PGC 1alpha and down stream genes . ^^^ To determine whether the regulation of FoxO 1 was Akt dependent , we next treated Akt 2 / and wild type mice with or without insulin . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
These properties are similar to those of FOXO 1 and FOXO 3 , and thus FOXO transcription factors seem to be regulated through a common mechanism by PKB in the growth factor signaling pathway . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In addition , oxidative stress or activation of the JNK pathway decreased the activity of Akt in HIT cells , leading to the decreased phosphorylation of Foxo 1 following nuclear localization . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Given that Akt and Skp 2 proteins are highly activated in human cancers due to the loss of phosphatase and tensin homolog ( PTEN ) , deregulation of the FOXO 1 protein appears to be a promising target for future drug discovery and cancer therapy . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
However , rapamycin potently activates AKT dependent signaling , an effect that overrides the downregulation of this pathway by insulin resistance and that causes phosphorylation of the AKT dependent transcription factor FOXO 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
C5b 9 induced endothelial cell proliferation and migration are dependent on Akt inactivation of forkhead transcription factor FOXO 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
These responses were not dependent on the phosphorylation status of Akt and FOXO 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
We show that CC formation follows a multistep progression of histopathological changes that are associated with significant alterations , including increased levels of phosphorylated AKT , FOXO 1 , GSK 3beta , mTOR , and ERK and increased nuclear levels of cyclin D 1 . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Consistent with these findings , we detected increased Akt activity and nuclear beta catenin in intestines of PTK 6 deficient mice and decreased nuclear localization of the Akt substrate FoxO 1 in villus epithelial cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Foxo 1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti related protein through the phosphatidylinositol 3 kinase ( PI3K ) / Akt signaling pathway , but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer activated transcript 3 ( STAT 3 ) . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Moreover , combined drug induced Akt deactivation was associated with a parallel decrease in phosphorylation of FoxO 1 transcription factor and in expression of antiapoptotic Bcl xL . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
The FOXO family of forkhead transcription factor Foxo 1 ( mouse FOXO 1 ) is a key regulator that stimulates the expression of gluconeogenic genes in the nucleus but is phosphorylated by Akt ( also known as protein kinase B ; PKB ) and translocated to the cytoplasm in response to insulin . ^^^ Although it has been widely accepted that the cellular signaling of insulin represses Foxo 1 function through Akt dependent phosphorylation , the molecular mechanism behind the modulation of Foxo 1 function by nutrient responses , including feeding or fasting , remains unknown in vivo . ^^^ We investigated the consequences of the nutritional changes in Akt mediated Foxo 1 phosphorylation and translocation in the liver using control C57BL / 6 and diabetic db / db mice . ^^^ Thus , we suggest that the accurate regulation of Foxo 1 via Akt dependent phosphorylation is required for physiological adaptation to different nutritional statuses . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Insulin stimulation of Akt and FOXO 1 phosphorylation was also significantly decreased with Intralipid and lactate infusions . ^^^ These data suggest that insulin ' s effect to suppress PDK 4 gene expression in skeletal muscle is impaired in insulin resistant states , and this may be due to impaired insulin signaling for stimulation of Akt and FOXO 1 phosphorylation . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Myostatin signaling reversed the IGF 1 / PI3K / AKT hypertrophy pathway by inhibiting AKT phosphorylation thereby increasing the levels of active FoxO 1 , allowing for increased expression of atrophy related genes . ^^^ Furthermore , increased Myostatin levels appear to antagonize hypertrophy signaling through regulation of the AKT FoxO 1 pathway . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
FoxO 1 gain of function paradoxically increased insulin sensitivity by promoting Akt phosphorylation , while FoxO 1 inhibition via siRNA decreased it . ^^^ We show that FoxO 1 regulation of Akt phosphorylation does not require DNA binding and is associated with repression of the pseudokinase tribble 3 ( Trb 3 ) , a modulator of Akt activity . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK 4 promoter activity , while coexpression of constitutively active FOXO1a or FOXO3a , which are mutated to alanine at the three phosphorylation sites for protein kinase B ( PKB ) , disrupts the ability of PKB alpha to inhibit promoter activity . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
These changes caused impaired activation of the PI 3 kinase / Akt survival signaling that resulted in reduced GSK 3 and FOXO1a inactivation . ^^^ BADGP reversed the glucosamine induced reduction in insulin stimulated phosphorylation of IR , IRS 1 , IRS 2 , Akt , GSK 3 , and FOXO1a . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
Encouragingly , recent studies demonstrate that small molecules can regulate FOXO1a , an Akt target , to suppress tumor growth , and FOXO1a is therefore a promising anticancer drug target . . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
In parallel , the effects of insulin on Akt activation , glycogen synthase kinase 3 , and FoxO1a phosphorylation , and glucose secretion were all significantly decreased in CYP2E1 overexpressing cells . ^^^
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q12778 and P31749	Pubmed	SVM Score :0.0
NA