| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that Akt also regulates the activity of FKHRL 1 , a member of the Forkhead family of transcription factors . ^^^ In the presence of survival factors , Akt phosphorylates FKHRL 1 , leading to FKHRL 1 ' s association with 14 3 3 proteins and FKHRL 1 ' s retention in the cytoplasm . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| A member of Forkhead family transcription factor , FKHRL 1 , is one of the downstream molecules of phosphatidylinositol 3 kinase Akt activation pathway in erythropoietin signal transduction . ^^^ Moreover , results showed that Akt kinase activated by EPO directly phosphorylated FKHRL 1 protein and that FKHRL 1 phosphorylation was completely dependent on PI3K activity as is the case for Akt . ^^^ In conjunction with the evidence that FKHRL 1 is expressed in normal human erythroid progenitor cells and erythroblasts , the results suggest that FKHRL 1 plays an important role in erythropoiesis as one of the downstream target molecules of PI3K Akt . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In addition , Epo treatment of erythroid progenitors induces phosphorylation of a member of the Forkhead family ( FH ) of transcription factors FKHRL 1 , downstream of activation of the Akt kinase . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Insulin like growth factor 1 induced phosphorylation of the forkhead family transcription factor FKHRL 1 is mediated by Akt kinase in PC 12 cells . ^^^ The Forkhead family transcription factor FKHRL 1 , a mammalian homolog of DAF 16 in the nematode Caenorhabditis elegans , is an inducer of apoptosis in its unphosphorylated form and was recently reported as a substrate of Akt kinases . ^^^ In this study , we characterized the phosphorylation of FKHRL 1 induced by IGF 1 in PC 12 cells and various neuronal cell types and examined the potential role of Akt in this regard . ^^^ IGF 1 rapidly induced the phosphorylation of Akt and FKHRL 1 in PC 12 cells . ^^^ The phosphorylation of Akt and FKHRL 1 induced by 10 nm IGF 1 was inhibited by the phosphatidylinositide 3 kinase ( PI3K ) inhibitors wortmannin ( 0 . 25 2 microm ) and LY 294002 ( 12 . 5 100 microm ) , but not by the MEK inhibitor PD 98059 ( 50 microm ) or the p 70 S6 kinase pathway inhibitor rapamycin ( 50 nm ) , suggesting that the phosphorylation of FKHRL 1 induced by IGF 1 is mediated by the PI3K pathway . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We showed that CISK acts downstream of the PI 3 kinase cascade in vivo and may function in parallel to Akt by phosphorylating Bad and the transcription factor FKHRL 1 . ^^^ |
|
| Interacting proteins: O43524 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 . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt phosphorylates Forkhead transcription factors such as FKHRL 1 , leading to FKHRL 1 ' s exit from the nucleus and the consequent shutoff of FKHRL 1 target genes . ^^^ We show here that SGK 1 , like Akt , promotes cell survival and that it does so in part by phosphorylating and inactivating FKHRL 1 . ^^^ However , SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL 1 . ^^^ These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL 1 by phosphorylating this transcription factor at distinct sites . ^^^ The efficient phosphorylation of these three sites on FKHRL 1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL 1 dependent transcription , thereby preventing FKHRL 1 from inducing cell cycle arrest and apoptosis . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Accumulated evidence indicates that IGF 1 , apart from regulating growth and development , protects neurons against cell death induced by amyloidogenic derivatives , glucose or serum deprivation via the activation of intracellular pathways implicating phosphatidylinositide 3 / Akt kinase , winged helix family of transcription factor FKHRL 1 phosphorylation or production of free radicals . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We find that the overexpression of FKHR [ S256A ] ( where Ser 256 > Ala ) blocks PKB activity in cells , preventing phosphorylation of the endogenous substrates FKHRL 1 and glycogen synthase kinase 3 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We show that , in this mutant , Akt is constitutively activated leading to FKHRL 1 phosphorylation and constitutive glycolytic activity . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| FKHRL 1 , a member of the Forkhead transcription factor family , is one of the downstream molecules of phosphatidylinositol 3 kinase Akt . ^^^ In this study we found that Akt and FKHRL 1 proteins were detectable in highly purified normal human megakaryocytes and that these molecules were actually phosphorylated by thrombopoietin ( TPO ) . ^^^ These results suggest that FKHRL 1 plays an important role in the cell cycle of megakaryocytic cells as one of the downstream target molecules of phosphatidylinositol 3 kinase Akt , presumably mediated through the activation or inactivation of cell cycle associated gene ( s ) . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Transforming growth factor beta enhances epithelial cell survival via Akt dependent regulation of FKHRL 1 . ^^^ A triple mutant of FKHRL 1 , in which all three Akt phosphorylation sites have been mutated ( TM FKHRL 1 ) , did not translocate to the cytoplasm in response to TGF beta . ^^^ In HaCaT keratinocytes , expression of dominant negative Akt prevented TGF beta induced 1 ) reduction of Forkhead dependent transcription , 2 ) FKHRL 1 phosphorylation , and 3 ) nuclear exclusion of FKRHL 1 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Our results indicate that Akt mediated signals , acting through the forkhead transcription factor FKHRL 1 , can regulate collagenase expression in WI 38 fibroblasts . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Similarly , induction of FasL by the Akt regulated forkhead transcription factor FKHRL 1 was dependent upon caspase and c Jun activation . ^^^ Taken together , these results indicate that the sequential activation of caspase 3 and c Jun participates in the induction of FasL under conditions of suppressed Akt signaling or FKHRL 1 activation and that FasL participates in a positive feedback loop to promote cell death under conditions of cellular stress . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Moreover , survival assays with the PtdIns 3 kinase inhibitor LY 294002 , active and dominant negative forms of Akt indicate that the phosphorylation of FKHRL 1 plays a role in neurotrophins mediated cell survival . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Forkhead factor FKHRL 1 binds in vitro to the three consensus sequences and can activate TGF beta 2 promoter in normal and Akt transformed cell lines . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| These effects correlated with inhibition of Akt activity and FKHRL 1 phosphorylation . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| BDNF increased the phosphorylation of the forkhead transcription factor FKHRL 1 through activation of the phosphatidylinositol 3 kinase ( PI3K ) / Akt signaling pathway , and the phosphorylation of the cyclic AMP response element binding protein ( CREB ) through activation of extracellular signal regulated kinase1 / 2 ( ERK1 / 2 ) . ^^^ Overexpression of GSK3beta did not affect BDNF induced phosphorylation of Akt , ERK1 / 2 , or FKHRL 1 , but abolished CREB phosphorylation induced by BDNF . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Insulin like growth factor 1 induced phosphorylation of transcription factor FKHRL 1 is mediated by phosphatidylinositol 3 kinase / Akt kinase and role of this pathway in insulin like growth factor 1 induced survival of cultured hippocampal neurons . ^^^ FKHRL 1 , a member of the Forkhead family of transcription factors possibly involved in cell cycle and apoptosis , is a downstream target of Akt in fibroblasts . ^^^ IGF 1 blocked the nuclear translocation of FKHRL 1 in hippocampal neurons and promoted survival in parallel to the phosphorylation of Akt and FKHRL 1 . ^^^ Similarly , the expression of constitutively active Akt in PC 12 cells increased the phosphorylation of FKHRL 1 and promoted survival , whereas the expression of kinase dead Akt attenuated IGF 1 mediated survival of PC 12 cells . ^^^ Taken together , these data reveal that endogenous FKHRL 1 is a downstream substrate of PI3K / Akt in IGF 1 receptor signaling in hippocampal neurons and suggest that the phosphorylation of this transcription factor may play an important role in the neuronal survival properties of IGF 1 . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| During the early stage of infection with pYV+ and pYV bacteria , Akt and its targets , glycogen synthase kinase 3 ( GSK 3 ) and forkhead transcription factor ( FKHRL 1 ) , became phosphorylated . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In the current study , we demonstrate that IGF 1 stimulates sustained activation of NF kappaB and Akt ; induces phosphorylation of the FKHRL 1 Forkhead transcription factor ; upregulates a series of intracellular anti apoptotic proteins including FLIP , survivin , cIAP 2 , A1 / Bfl 1 , and XIAP ; and decreases Apo2L / TRAIL sensitivity of MM cells . ^^^ In contrast , IL 6 does not cause sustained NF kappaB activation , induces less pronounced Akt activation and FKHRL 1 phosphorylation than IGF 1 , and increases the expression of only survivin . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis revealed that Cl F araA induced a dose and time dependent downregulation of Bcl 10 ( L ) and Mcl 1 proteins , and a dose and time dependent dephosphorylation of Akt and its downstream effectors ( Bad , FKHRL 1 ) , particularly in vivo . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In both cell lines , constitutive activation of the PI 3 K / Akt / FKHRL 1 , mTOR / P70 ( S6K ) and MAPK pathways was detected . ^^^ LY 294002 inhibited phosphorylation of Akt , FKHRL 1 and P 70 ( S6K ) but had no effect on ERK1 / 2 phosphorylation , indicating that the PI 3 K and MAPK pathways are independent . ^^^ IGF 1 but not IL 6 increased phosphorylation of Akt , FKHRL 1 and P 70 ( S6K ) . ^^^ In three of them including the two patients with PCL , constitutive phosphorylation of Akt , FKHRL 1 and P 70 ( S6K ) was present , inhibited by LY 294002 and enhanced by IGF 1 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Finally , adenoviral mediated expression of dominant negative AKT activated FKHRL 1 and induced expression of Bim . ^^^ These data suggest that IGF 1 signaling via AKT promotes survival of cerebellar granule neurons by blocking the FKHRL 1 dependent transcription of Bim , a principal effector of the intrinsic death signaling cascade . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| A member of the Forkhead transcription factor family , FKHRL 1 , lies downstream of the phosphatidylinositol 3 kinase Akt activation pathway in cytokine signaling . ^^^ Because the phosphatidylinositol 3 kinase Akt activation pathway is required for BCR ABL mediated transformation and survival signaling in chronic myelogenous leukemia ( CML ) , in this study we examined the involvement of FKHRL 1 in the BCR ABL mediated signaling pathway . ^^^ To demonstrate this hypothesis , we generated a tamoxifen inducible `` active FKHRL 1 ' ' FKHRL 1 TM ( a triple mutant of FKHRL 1 , in which all three Akt phosphorylation sites have been mutated ) , estrogen receptor system in the KCL 22 cell line . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In this report , we investigated the role of PDGF induced Akt in regulating forkhead domain protein FKHRL 1 in glomerular mesangial cells . ^^^ Expression of dominant negative Akt by adenovirus mediated gene transfer blocked PDGF induced FKHRL 1 phosphorylation . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We have previously demonstrated that collagenase expression is under positive regulation by the transcription factor FKHRL 1 and that this transcription factor is under negative regulation by the phosphatidylinositol 3 kinase ( PI3K ) / Akt ( PKB ) pathway . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Overexpressed IRS 3 as well as IRS 1 enhanced phosphoinositide ( PI ) 3 kinase activity in response to insulin and increased phosphorylation of protein kinase B ( PKB ) at S 473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL 1 on T 32 in both insulin untreated and treated states . ^^^ Treatment of these cells with a PI 3 kinase inhibitor LY 294002 suppressed apoptosis inhibitory effects of IRS 1 and IRS 3 as well as the phosphorylation of PKB and FKHRL 1 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Using different in vitro systems , we demonstrate that 3 alternative pathways independently lead to Epo induced activation of PI 3 kinase and phosphorylation of its downstream effectors , Akt , FKHRL 1 , and P70S6 kinase : through direct association of PI 3 kinase with the last tyrosine residue ( Tyr 479 ) of the Epo receptor ( EpoR ) , through recruitment and phosphorylation of Gab proteins via either Tyr 343 or Tyr 401 of the EpoR , or through phosphorylation of IRS 2 adaptor protein . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Examination of signalling pathways involved in apoptosis revealed that phosphorylation of PKB and the forkhead transcription factor , FKHRL 1 , was induced by IGFs , but that phosphorylation was blocked by IGFBP 5 and IGFBP 3 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In MDA 468 / PTEN but not in vector controls , treatment with ZD 1839 inhibited P Akt levels , induced relocalization of the Forkhead factor FKHRL 1 to the cell nucleus , and increased FKHRL 1 dependent transcriptional activity . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| These pathways encompass the modulation of Akt , the forkhead transcription factor FKHRL 1 , mitochondrial membrane potential , caspase activities and cellular energy metabolism , but remain independent of intracellular pH and mitogen activated protein kinases . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt phosphorylation increased after hyperthermia and was accompanied by an increased phosphorylation of two substrates , GSK 3 and FKHRL 1 , in both brain areas , with a major effect in the cerebellum . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The Forkhead family transcription factor FKHRL 1 is an inducer of apoptosis in its unphosphorylated form and was recently reported to be a substrate of Akt kinase . ^^^ Transfection experiments revealed that a kinase inactive mutant of Akt or a triple mutant ( TM ) of FKHRL 1 , in which all three of the putative Akt phosphorylation sites were converted to alanine , was unable to phosphorylate the FKHRL 1 protein in cells treated with cisplatin . ^^^ Transfection with the kinase inactive mutant of Akt or TM of FKHRL 1 induced the activity of the Fas ligand promoter in Caov 3 cells . ^^^ Our findings suggest that cisplatin causes the phosphorylation of FKHRL 1 via a phosphatidylinositol 3 kinase / Akt cascade , and inhibition of this cascade sensitizes ovarian cancer cells to cisplatin . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The level of phosphorylated FKHRL 1 , a transcription factor phosphorylated by PKB , decreased in irradiated oligodendrocytes . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The phosphorylation of Akt and its downstream target , FKHRL 1 , induced by IGF 1 was rapid and sustained while that of MAPK was transient . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Stromal cell derived factor 1alpha ( SDF 1alpha ; CXCL 12 ) stimulation of breast cancer cells resulted in phosphoinositide 3 kinase ( PI 3K ) activation , AKT phosphorylation , and activation of the FKHRL 1 transcription factor . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| PRL stimulation of W 53 cells resulted in Akt translocation to the nucleus , phosphorylation of FKHRL 1 transcription factor , and its nuclear exclusion . ^^^ In contrast , induced expression of Akt CAAX Box caused inhibition of FKHRL 1 phosphorylation . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Overexpression of a constitutively active ( phosphorylation resistant ) form of FKHRL 1 ( TMFKHRL 1 ) resulted in increased Mn SOD expression , suggesting that the negative effect of PI3K Akt involves attenuation of forkhead activity . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We identify for the first time the Forkhead box protein FOXO3a ( formerly termed FKHRL 1 ) , which is inactivated by Akt , as a key regulator of ERalpha gene transcription . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| AKT was dispensable for p 53 dependent suppression of FKHRL 1 . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| METHODS AND RESULTS : Adenovirus expressing the constitutively active FKHRL 1 ( FKHRL 1 TM ; triple mutant ) with 3 Akt phosphorylation sites mutated was transfected to subconfluent VSMCs . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| METHODS : Human umbilical venous endothelial cells were treated with Hcy , and / or LY 294002 , okadaic acid , peroxovanadate ( PV ) , antisense Akt , phosphorylation of Akt and FKHRL 1 proteins . p 27 ( kip 1 ) protein levels were measured with Western blotting , and Akt kinase activity and cell cycle were measured with immunoprecipitation and flow cytometry , respectively . ^^^ RESULTS : We demonstrate that Hcy induces dephosphorylation of Akt and FKHRL 1 and upregulates the cyclin dependent kinase inhibitors p 27 ( kip 1 ) in a time and dose dependent manner . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Activation of Akt ( PKB ) and suppression of FKHRL 1 in mouse and rat oocytes by stem cell factor during follicular activation and development . ^^^ In this study , by using ovaries and isolated oocytes from postnatal mice and rats , we demonstrated for the first time that components of the PI 3 kinase pathway , the serine / threonine kinase Akt ( PKB ) which enhances cellular proliferation and survival , and an Akt substrate FKHRL 1 which is a transcription factor that leads to apoptosis and cell cycle arrest , are expressed in mammalian oocytes . ^^^ By using an in vitro oocytes culture system , we found that oocytes derived Akt and FKHRL 1 are regulated by SCF . ^^^ Treatment of cultured oocytes with SCF can not only rapidly phosphorylate and activate Akt , but also simultaneously phosphorylate and may therefore functionally suppress FKHRL 1 , through the action of PI 3 kinase . ^^^ Together with our in situ hybridization and immunohistochemistry data that Akt and FKHRL 1 are mostly expressed in oocytes in primordial and primary ovaries and reports that FKHRL 1 gene deficient mice exhibited excessive activation from primordial to primary follicles as well as enlarged oocyte sizes , we suppose that in mammalian oocytes , actions of granulosa cell derived SCF on primordial to primary follicle transition and subsequent follicle development may involve activation of Akt and inhibition of FKHRL 1 activities in oocytes . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The activation of PKB by RET / PTC blocked the activity of the forkhead transcription factor , FKHRL 1 , but a Y315F mutant of PKB failed to inhibit FKHRL 1 activity . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Lysates of cells were subjected to Western blot analyses of IKK alpha , IKK beta , p 65 ( RelA ) subunit of nuclear factor kappaB ( NF kappaB ) , total Akt , phospho Akt ( Ser 473 ) , and phospho FKHR ( Thr 24 ) / phosphor FKHRL 1 ( Thr 32 ) . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In addition , we show that Galpha12QL stimulates the phosphorylation of forkhead transcription factor FKHRL 1 via AKT in a PDGFRalpha and PI3K dependent manner . ^^^ Since AKT promotes cell growth by blocking the transcription of antiproliferative genes through the inhibitory phosphorylation of forkhead transcription factors , our results describe for the first time a PDGFRalpha dependent signaling pathway involving PI3K AKT FKHRL 1 , regulated by Galpha12QL in promoting cell growth . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| FKHRL 1 activity was negatively regulated by phosphorylation catalyzed by Akt , an anti apoptotic kinase . ^^^ Akt upregulation by adenoviral gene transfer inhibited Abeta induced FKHRL 1 activation and bim induction . ^^^ Suppression of PP2A activity by RNA interference or a specific inhibitor , okadaic acid , effectively suppressed Abeta induced Akt inactivation and FKHRL 1 activation , leading to an attenuation of bim expression and cell death in CECs . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| We hypothesized that inhibition of the transcription factor FKHRL 1 by the PI3K / protein kinase B pathway attenuates hiNOS promoter induction by bacterial lipopolysaccharide and interferon gamma ( LPS / IFN gamma ) . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here we show that the PKB regulated Forkhead transcription factor FOXO3a ( also known as FKHR L 1 ) protects quiescent cells from oxidative stress by directly increasing their quantities of manganese superoxide dismutase ( MnSOD ) messenger RNA and protein . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt activation promotes degradation of tuberin and FOXO3a via the proteasome . ^^^ Expression of activated Akt triggered proteasome dependent declines in the protein levels of the Akt substrates tuberin , FOXO 1 , and FOXO3a . ^^^ |
|
| Interacting proteins: O43524 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 . ^^^ Transfection of endothelial cells with either a dominant negative or an `` Akt resistant ' ' / constitutively active FOXO3a mutant reversed the 11 , 12 EET induced down regulation of p27Kip1 , whereas transfection of a constitutive active Akt decreased p27Kip1 expression independently of the presence or absence of 11 , 12 EET . ^^^ Transfection of CYP2C9 elicited endothelial cell proliferation and this effect was inhibited in cells co transfected with CYP2C9 and either a dominant negative Akt or constitutively active FOXO3a . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The Akt regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase 8 inhibitor FLIP . ^^^ Here we examined the role of the forkhead transcription factor FOXO3a , a downstream target of Akt , in controlling FLIP regulation in endothelial cells . ^^^ FOXO3a nuclear translocation was regulated by Akt in human umbilical vein endothelial cells . ^^^ These data suggest that FOXO3a is a downstream target of Akt in endothelial cells that can promote apoptosis via FLIP down regulation and activation of the extrinsic apoptotic pathway . . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Constitutive activation of Akt promotes senescence like arrest of cell growth via a p53 / p21 dependent pathway , and inhibition of forkhead transcription factor FOXO3a by Akt is essential for this growth arrest to occur . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| To further study survival signaling by NPMALK , we generated Ba / F3 cell lines with either inducible or constitutive expression of NPM ALK and examined the regulation of the AKT target FOXO3a . ^^^ We hypothesized that NPM ALK signaling through phosphoinositol 3 kinase ( PI 3 kinase ) and AKT would regulate FOXO3a , a member of the forkhead family of transcription factors , thereby stimulating proliferation and blocking programmed cell death in NPM ALK transformed cells . ^^^ In Ba / F3 cells with induced or constitutive expression of NPM ALK , concomitant AKT activation and phosphorylation of its substrate , FOXO3a , was observed . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrate that FLT 3 ITD expression in Ba / F3 cells results in activation of Akt and concomitant phosphorylation of the Forkhead family member Foxo3a . ^^^ |
|
| Interacting proteins: O43524 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: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Nuclear exclusion of the forkhead transcription factor FOXO3a by protein kinase Akt contributes to cell survival . ^^^ We investigated the pathological relationship between phosphoylated Akt ( Akt p ) and FOXO3a in primary tumors . ^^^ Surprisingly , FOXO3a was found to be excluded from the nuclei of some tumors lacking Akt p , suggesting an Akt independent mechanism of regulating FOXO3a localization . ^^^ We provide evidence for such a mechanism by showing that IkappaB kinase ( IKK ) physically interacts with , phosphorylates , and inhibits FOXO3a independent of Akt and causes proteolysis of FOXO3a via the Ub dependent proteasome pathway . ^^^ Cytoplasmic FOXO3a correlates with expression of IKKbeta or Akt p in many tumors and associates with poor survival in breast cancer . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress through protein kinase B coupled to FOXO3a and mitochondrial membrane potential . ^^^ |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt regulates the sub cellular localization of FOXO3a by phosphorylation thereby preventing the protein to translocate to the nucleus and regulate transcription . ^^^ Constitutive Akt activation is frequently correlated with cytoplasmatic FOXO3a in breast tumors and this is associated with decreased patient survival . ^^^ Cell 2004 ; 117 : 225 237 ) FOXO3a was found in the cytoplasm in the absence of activated Akt . ^^^ |
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| Interacting proteins: O43524 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 . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Vpr inhibited the ability of insulin or its downstream protein kinase Akt to change the intracellular localization of Foxo3a preferentially to the cytoplasm . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| However , such deficiency had no effect on the basal expression or activity of Akt , FoxO3a , p 53 , and c myc that regulate the transcription of gadd45alpha gene positively or negatively . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Remarkably , altered NF kappaB activity elicited by GR overexpression correlated with a dramatic decrease in the protein levels of DeltaNp 63 in tooth epithelia without affecting Akt , BMP 4 , or Foxo3a . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling . ^^^ In cardiac myocyte cultures , transduction with constitutively active Akt or treatment with IGF suppressed atrogin 1 mRNA expression , whereas transduction with FOXO3a stimulated its expression . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt / FOXO3a signaling modulates the endothelial stress response through regulation of heat shock protein 70 expression . ^^^ Gene transfer of FOXO3a , a downstream target of Akt in endothelial cells , significantly suppressed both basal and stress induced HSP 70 protein expression . ^^^ Our results identify HSP 70 as a new antiapoptotic target of Akt FOXO3a signaling in endothelial cells that controls viability through modulation of the stress induced intrinsic cell death pathway . . ^^^ |
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| Interacting proteins: O43524 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 . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| SCF induced a rapid and transient phosphorylation of Akt ( protein kinase B ) and FOXO3a . ^^^ Because apoptosis is abnormally reduced in bim / mast cells , these data provide evidence that Akt mediated inhibition of FOXO3a and its transcription target Bim provides an important mechanism by which SCF acts to prevent apoptosis in mast cells . . ^^^ |
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| Interacting proteins: O43524 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 . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here , we show that phosphorylation of 14 3 3 by JNK releases the proapoptotic proteins Bad and FOXO3a from 14 3 3 and antagonizes the effects of Akt signaling . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Induction of androgen receptor expression by phosphatidylinositol 3 kinase / Akt downstream substrate , FOXO3a , and their roles in apoptosis of LNCaP prostate cancer cells . ^^^ Here we provide the first linkage by the identification of Forkhead transcription factor FOXO3a , the PI3K / Akt downstream substrate , as a positive regulator for the induction of AR gene expression . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here we further characterize this signaling defect and report that a p110delta selective small molecule inhibitor mirrors the effect of genetic inactivation of p110delta in BCR signaling . p110delta activity is indispensable for BCR induced DNA synthesis and phosphorylation of Akt / protein kinase B ( PKB ) , forkhead transcription factor / forkhead box O3a ( FOXO3a ) , and p 70 S6 kinase ( p 70 S6K ) , with modest effects on the phosphorylation of glycogen synthase kinase 3 alpha / beta ( GSK3alpha / beta ) and extracellular signal regulated kinase ( Erk ) . ^^^ Resting B cells with inactive p110delta fail to enter the cell cycle , correlating with an incapacity to up regulate the expression of cyclins D 2 , A , and E , and to phosphorylate the retinoblastoma protein ( Rb ) . p110delta is also critical for interleukin 4 ( IL 4 ) induced phosphorylation of Akt / PKB and FOXO3a , and protection from apoptosis . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| In MET positive DLBCL cells , HGF induces MEK dependent activation of ERK and PI3K dependent phosphorylation of PKB , GSK 3 , and FOXO3a . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Tumors produced by subcutaneous injection of Akt transformed keratinocytes showed increased Foxo3a phosphorylation , but no major alterations in p 21 ( Cip1 / WAF1 ) , p 27 ( Kip 1 ) or mdm 2 expression and / or localization . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Constitutive activation of Akt phosphorylated and inhibited the transcription factor Foxo3a . ^^^ Restored Foxo3a activity reversed Flt 3 ITD mediated growth properties and dominant negative Akt prevented Flt 3 ITD mediated cytokine independence . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Paclitaxel induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c Jun NH 2 terminal kinase and Akt . ^^^ We have previously shown that apoptosis of breast cancer cells in response to paclitaxel is mediated by induction of FOXO3a expression , a transcription factor downstream of the phosphatidylinositol 3 kinase / Akt signaling pathway . ^^^ To further investigate its mechanism of action , we treated MCF 7 cells with paclitaxel and showed a dose dependent increase in nuclear localization of FOXO3a , which coincided with decreased Akt signaling but increased c Jun NH 2 terminal kinase 1 / 2 ( JNK1 / 2 ) , p 38 , and extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) activity . ^^^ SP 600125 reversed Akt inhibition and abolished FOXO3a nuclear accumulation in response to paclitaxel . ^^^ Moreover , conditional activation of JNK mimicked paclitaxel activity and led to dephosphorylation of Akt and FOXO3a . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Exposure to 20 mM glucose resulted in decreased Akt phosphorylation and enhanced nuclear translocation of forkhead box O3a ( FOXO3a ) . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis indicated that KP 372 1 decreased the phosphorylation of AKT on both Ser ( 473 ) and Thr ( 308 ) ; abrogated the phosphorylation of p70S6 kinase , BAD , and Foxo3a via PI3K / AKT signaling ; and down regulated expression of PIM 1 through direct inhibition of FLT 3 . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Group 1 metabotropic receptor neuroprotection requires Akt and its substrates that govern FOXO3a , Bim , and beta catenin during oxidative stress . ^^^ Closely coupled to the robust neuroprotection by mGluRI activation are the inhibitory phosphorylation and prevention of caspase 3 cleavage of the Forkhead transcription factor FOXO3a , the down regulation of Bim expression , and the protection of beta catenin by Akt 1 against phosphorylation and degradation to promote its translocation from the cytoplasm to the nucleus and allow it to assist with a `` pro survival ' ' cellular program . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| Our results suggest that Puma , together with another BH 3 only member , Bim , function as FOXO3a downstream targets to mediate a stress response when PI3K / Akt signaling is down regulated . . ^^^ |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O43524 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|