| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.73643251 |
| Here , we show that Akt bound directly to and phosphorylated p 27 ( Kip 1 ) . 0.73643251^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Exposure of CNE 2 cells to ceramide resulted in a dose dependent up regulation of the cyclin dependent kinase inhibitor p 27 and a decrease of phospho Akt without reduced expression of total AKT protein . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The phosphoinositide 3 kinase / Akt pathway regulates cell cycle progression of HL 60 human leukemia cells through cytoplasmic relocalization of the cyclin dependent kinase inhibitor p 27 ( Kip 1 ) and control of cyclin D 1 expression . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition of active Ras by farnesylthiosalicylic acid led to attenuation of the Raf MEK ERK and phosphoinositide 3 kinase Akt glycogen synthase 3 ( GSK 3 ) pathways , to reduction in cyclin D 1 , phospho retinoblastoma , and E2F , and to increase in the cyclin dependent kinase inhibitor p 27 and in retinoblastoma binding protein 1 , an inhibitor of E2F transcriptional activity . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Taken together , our results suggest that in contact inhibited HUVECs , increased phosphatase activity suppressed the ERK and PI 3 K / Akt pathways , resulting in exit from the cell cycle by down regulation of cyclin D 1 , cyclin E , and cyclin A and by up regulation of p 27 ( kip 1 ) . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| However , treatment with LY 294002 , an inhibitor of phosphatidylinositol 3 kinase ( PI3K ) , inhibited basal Akt activity , up regulated p 27 , and recruited cells in G ( 1 ) . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression . ^^^ Furthermore , expression of the p 27 ( Kip 1 ) cell cycle regulator was diminished in LNAI cells , consistent with the notion that AKT directly inhibits AFX / Forkhead mediated transcription of p 27 ( Kip 1 ) . ^^^ Together , these data implicate increased AKT activity in prostate tumor progression and androgen independence and suggest that diminished p 27 ( Kip 1 ) expression , which has been repeatedly associated with prostate cancer progression , may be a consequence of increased AKT activity . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| In accord with this is the observation that activation of M+ Akt : ER * led to decreased expression of the cyclin dependent kinase inhibitor p27Kip1 with a concomitant increase in cyclin dependent kinase 2 activity . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| BCR / ABL regulates expression of the cyclin dependent kinase inhibitor p27Kip1 through the phosphatidylinositol 3 Kinase / AKT pathway . ^^^ Transient expression of an activated mutant of AKT was found to decrease expression of p 27 ( Kip 1 ) , even when PI3K was inhibited by LY 294002 . ^^^ Overall , these data are consistent with a model in which BCR / ABL suppresses p 27 ( Kip 1 ) protein levels through PI3K / AKT , leading to accelerated entry into S phase . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| AFX like Forkhead transcription factors mediate cell cycle regulation by Ras and PKB through p27kip1 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt serine threonine kinase regulates platelet derived growth factor induced DNA synthesis in glomerular mesangial cells : regulation of c fos AND p 27 ( kip 1 ) gene expression . ^^^ Expression of dominant negative Akt increased p 27 ( kip 1 ) protein and resulted in inhibition of CDK 2 activity . ^^^ The increase in p 27 ( kip 1 ) expression in response to Akt kinase inhibition was due to increased transcription of the p 27 ( kip 1 ) gene . p 27 ( kip 1 ) transcription similarly was decreased by expression of constitutively active Akt kinase in mesangial cells . ^^^ These data provide the first evidence that Akt kinase regulates PDGF induced DNA synthesis by regulating CDK 2 activity and define Akt mediated inhibition of transcription of p 27 ( kip 1 ) as one of the mechanisms for PDGF induced DNA synthesis in mesangial cells . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| These data imply that : ( a ) modulation of both p 27 and cyclin D 1 are required for the growth arrest that results from blockade of the ErbB 2 kinase ; and ( b ) ErbB 2 overexpressing cells use both MAPK and PI3K / Akt to modulate p 27 and cyclin D 1 and , hence , subvert the G ( 1 ) to S transition . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Under the lowered O 2 conditions , we noted a remarkable increase in the percentage of large sized colonies , activation of cell cycle progression factors , phosphorylation of Akt , and downregulation of the cell cycle inhibitor p27Kip1 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Involvement of Akt / protein kinase B in up regulation of p 21 ( WAF1 / CIP1 ) but not p 27 ( KIP 1 ) . ^^^ Overexpression of dominant negative Akt inhibited the decorin mediated induction of p 21 and cyclin A , but had no effect on p 27 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| 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: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| During the chronic stage of androgen deprivation , androgen independent proliferation correlated with diminished p 27 ( kip 1 ) protein levels , whereas PI3K and Akt activity remained elevated . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Furthermore , ectopic expression of a constitutively active form of AKT blocked the cell cycle arrest and apoptosis triggered by anti IgM and also abrogated down regulation of cyclin D 2 and up regulation of p 27 ( Kip 1 ) expression induced by BCR engagement . ^^^ These results indicate that BCR activation targets p 27 ( Kip 1 ) and cyclin D 2 to mediate cell cycle arrest and apoptosis and that down regulation of PI 3 K / AKT activity post BCR stimulation is necessary for these to occur . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| CD 28 costimulation mediates down regulation of p27kip1 and cell cycle progression by activation of the PI3K / PKB signaling pathway in primary human T cells . ^^^ These results show that the PI3K PKB pathway links CD 28 to cell cycle progression and suggest that p 27 ( kip 1 ) integrates mitogenic MEK and PI3K dependent signals from TCR and CD 28 in primary T lymphocytes . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| IGF 1 induces NIH 3T3 cell proliferation and survival by activating the kinase akt , which in turn inhibits various apoptotic mediators and the forkhead family of transcription factors , which mediate expression of p 27 ( kip 1 ) . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt also inhibits tuberin mediated degradation of p 27 ( kip 1 ) , thereby promoting CDK 2 activity and cellular proliferation . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| PKB / Akt mediates cell cycle progression by phosphorylation of p 27 ( Kip 1 ) at threonine 157 and modulation of its cellular localization . ^^^ We have shown a novel mechanism of Akt mediated regulation of the CDK inhibitor p 27 ( kip 1 ) . ^^^ Blockade of HER2 / neu in tumor cells inhibits Akt kinase activity and upregulates nuclear levels of the CDK inhibitor ( Kip 1 ) . ^^^ Recombinant Akt and Akt precipitated from tumor cells phosphorylated wild type p 27 in vitro . p 27 contains an Akt consensus RXRXXT ( 157 ) D within its nuclear localization motif . ^^^ Active ( myristoylated ) Akt phosphorylated wild type p 27 in vivo but was unable to phosphorylate a T157A p 27 mutant . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Immunobiot analyses indicated that G 1 arrest induced by the subapoptogenic doses of MSeA was associated with increased expression of p27kip1 and p21cip1 , but apoptosis was accompanied by dose dependent decreases of phosphorylation of protein kinase AKT and extracellular signal regulated kinase ( ERK1 / 2 ) in the absence of any phosphorylation change in p 38 mitogen activated protein kinase ( p38MAPK ) and c Jun NH 2 terminal kinase ( JNK1 / 2 ) . ^^^ In contrast , selenite exposure caused S phase arrest and caspase independent apoptotic DNA fragmentation , which were associated with decreased expression of p27kip1 and p21cip1 and increased phosphorylation of AKT , JNK1 / 2 , and p38MAPK . ^^^ Taken together , exposure of DU 145 cells to MSeA versus selenite induced differential patterns of cell cycle arrest and apoptosis execution as well as distinct patterns of effects on AKT , ERK1 / 2 , JNK1 / 2 , and p38MAPK phosphorylation and p27kip1 and p21cip1 expression . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Novel p 27 ( kip 1 ) C terminal scatter domain mediates Rac dependent cell migration independent of cell cycle arrest functions . ^^^ Furthermore , Rac GTPase was necessary for p 27 dependent migration but alone was insufficient for HepG 2 cell migration . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Subcellular localization of proteins was determined by immunofluorescent staining and expression of cyclin dependent kinase 4 ( Cdk 4 ) , p 27 ( Kip 1 ) ( p 27 ) , phosphatidylinositol 3 ( PI 3 ) kinase , protein kinase B / Akt ( Akt ) , and beta actin was analyzed by immunoblot . ^^^ |
|
| Interacting proteins: P46527 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 . ^^^ These results indicate that EET induced endothelial cell proliferation is associated with the phosphatidylinositol 3 kinase / Akt dependent phosphorylation and inactivation of FOXO factors and the subsequent decrease in expression of the cyclin dependent kinase inhibitor p27Kip1 . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Pharmacological blockade of other kinases , such as p42 / 44 , p 38 , and protein kinase A or C , did not influence the mechanosensitive gene regulation . p27Kip1 downregulation and cell cycle entry were , however , prevented by overexpression of a constitutively inactive form of Akt or constitutively active forms of forkhead transcription factors . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemistry for EGFR , activated EGFR , phosphorylated Akt , phosphorylated ERK , p 27 ( Kip 1 ) , and beta catenin was also performed . ^^^ Loss of immunohistochemical staining for activated EGFR , phosphorylated Akt , and phosphorylated ERK in cancer cells was observed in some patients after treatment . p 27 ( Kip 1 ) was absent in the cancer cells of most pretreatment biopsies ; two patients showed a marked increase in staining for nuclear p 27 ( Kip 1 ) after treatment with ZD 1839 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Chakravarthy et al . , ( 2000 , J Biol Chem 275 : 35942 35952 . ) previously found that IGF 1 stimulated proliferation of primary satellite cells was associated with the activation of phosphatidylinositol 3 ' kinase ( PI3K ) / Akt and the downregulation of a cell cycle inhibitor p27Kip1 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P46527 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 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| When phosphorylation of PKB was solely blocked by wortmannin , p 27 ( kip 1 ) protein level was increased . ^^^ CONCLUSION : S phase delay induced by overexpression of integrin beta 1 subunit is attributed to the decrease of PKB phosphorylation and subsequent increases of p 21 ( cip 1 ) and p 27 ( kip 1 ) proteins , and may be involved in the unoccupied alpha5beta1 because of lack of its ligands . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The current study was designed to determine whether adenosine 3 ' , 5 ' monophosphate ( cAMP ) antagonizes FGF 2 by inhibiting PI 3 kinase / Akt pathways , thus leading to regulation of cyclin dependent kinase 4 ( Cdk 4 ) and p 27 ( Kip 1 ) ( p 27 ) expression . ^^^ Subcellular localization of proteins was determined by immunofluorescent staining and expression of Cdk 4 , p 27 , PI 3 kinase , Akt , and beta actin was analyzed by immunoblot analysis . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| PKB triggers a network that positively regulates G1 / S cell cycle progression through inactivation of GSK 3 beta , leading to increased cyclin D 1 , and inhibition of Forkhead family transcription factors and the tumor suppressor tuberin ( TSC 2 ) , leading to reduction of p27Kip1 . ^^^ The identification of p21Waf1 / Cip1 and p27Kip1 as novel substrates of PKB provided new insights into mechanisms whereby hyperactivation of this lipid signaling pathway may lead to cell cycle deregulation in human cancers . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| We have previously identified that carboxyl terminal threonine 198 ( Thr 198 ) in p27Kip1 is a novel phosphorylation site and that Akt is associated with the phosphorylation at the site ( Fujita , N . , Sato , S . , Katayama , K . , and Tsuruo , T . ( 2002 ) J . ^^^ These results indicate that RSKs play a crucial role in cell cycle progression through translocation of p27Kip1 , in addition to Akt , to the cytoplasm in a phosphorylation and 14 3 3 binding dependent manner . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| To ectopically express these proteins we exploited the finding that the p 27 ( kip 1 ) mRNA was efficiently translated in the face of mTOR inhibition irrespective of AKT activity . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The dose of Pten affects key downstream targets such as Akt , p 27 ( Kip 1 ) , mTOR , and FOXO 3 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| In addition , caffeine did not affect p16INK4 or p27Kip1 protein levels , but inhibited the phosphorylation of protein kinase B ( Akt ) and glycogen synthase kinase 3beta . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Vascular smooth muscle cell ( VSMC ) proliferation , apoptotic cell death , together with Akt induction , telomerase activity , p27kip1 , and endothelial nitric oxide synthase ( eNOS ) expression was assessed in isolated arteries . ^^^ In arteries from old rats , Akt modulated cell cycle check points like telomerase activity and p27kip1 expression were decreased and increased , respectively , compared with adults . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| We found that ARF antagonized protein kinase B ( PKB ) / Akt mediated p27Kip1 phosphorylation and increased p 27 stability in HER2 / neu overexpressing cells . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt dependent T 198 phosphorylation of cyclin dependent kinase inhibitor p27kip1 in breast cancer . ^^^ Using this antibody , we demonstrate that : ( 1 ) endogenous p 27 ( kip 1 ) is phosphorylated at T 198 in 4 breast cancer cells lines ( MCF 7 , MDA MB 231 , MDA MB 436 and MDA MB 468 ) ; ( 2 ) T 198 phosphorylation is increased in breast cancer cells compared with normal mammary epithelial cells ( HMEC ) ; ( 3 ) T 198 phosphorylated p 27 ( kip 1 ) is exclusively cytoplasmic ; ( 4 ) T 198 phosphorylation is dependent on the activity of the PI3K PKB / Akt pathway , being it drastically reduced by the pharmacological PI3K inhibitor LY 294002 or stimulated by the constitutive activation of PKB / Akt . ^^^ Finally , in primary human breast carcinomas , cytoplasmic accumulation of T 198 phosphorylated p 27 ( kip 1 ) parallels Akt activation . ^^^ We conclude that in breast cancer cells p 27 ( kip 1 ) is phosphorylated at T 198 in a PI3K / Akt dependent manner and that this phosphorylation may contribute to p 27 ( kip 1 ) cytoplasmic mislocalization observed in breast cancer . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cytoplasmic mislocalization of p27Kip1 protein is associated with constitutive phosphorylation of Akt or protein kinase B and poor prognosis in acute myelogenous leukemia . ^^^ It was shown that Akt or protein kinase B ( Akt / PKB ) dependent phosphorylation of p27Kip1 led to the cytoplasmic mislocalization of p27Kip1 , suggesting the potential abrogation of its activity . ^^^ Here , we evaluated the localization of p27Kip1 protein in leukemic blasts in relation to Akt / PKB phosphorylation and clinical outcomes in acute myelogenous leukemia ( AML ) . ^^^ Cytoplasmic mislocalization of p27Kip1 was significantly associated with the constitutive serine ( 473 ) Akt / PKB phosphorylation in AML cells ( P < 0 . 05 ) . ^^^ Transfection of U 937 cells with an expression construct encoding the constitutively active form of Akt / PKB resulted in a remarkable increase in the levels of cytoplasmic p27Kip1 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cell cycle distribution and cell cycle regulator proteins p 27 ( Kip 1 ) and cyclin D 1 , together with the PI 3 K / Akt pathway , mitogen activated protein kinases and cleaved caspase 3 and caspase 9 , were evaluated . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma . ^^^ As the cyclin dependent kinase ( CDK ) inhibitor p 27 ( Kip 1 ) ( p 27 ) is usually not expressed in ALCL , we hypothesized that activated Akt ( pAkt ) phosphorylates p 27 resulting in increased p 27 proteolysis and cell cycle progression . ^^^ These findings implicate that Akt activation promotes cell cycle progression through inactivation of p 27 in ALCL . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The enhanced CQ dependent loss of functional HER 2 from the cell surface resulted in sustained inactivation of the serine / threonine kinase Akt , upregulation of p27Kip1 protein and inhibition of cyclin E / Cdk2 activity . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| For example , inhibitors of MEK and phosphatidylinositol 3 kinase induced p 27 expression primarily in G 1 phase , while inhibitors of AKT activity stimulated these levels primarily in S phase . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| However , cyclin D 1 was positive in 69 % of Akt expressing areas , whereas p 27 was positive in 30 % only . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| At the level of the cell cycle machinery , RAF and AKT cooperated to induce cyclin D 1 and repress p 27 ( Kip 1 ) expression . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| We have studied mechanisms of Akt mediated phosphorylation and regulation of cellular localization of p 27 . ^^^ Akt phosphorylates Thr 157 in p 27 and retains it in the cytosol . ^^^ In cells arrested in G ( 1 ) and then synchronized to enter into S phase , Akt mediated phosphorylation of Thr 157 p 27 occurred in the cytosol during G ( 1 ) phase of the cell cycle . ^^^ Both T157A and S10A p 27 mutants localized in the nucleus in all phases of the cell cycle regardless of the expression of active Akt . ^^^ Leptomycin B inhibited cytosolic Thr 157 P p 27 staining , implying that CRM 1 dependent nuclear export is required for Akt mediated Thr 157 phosphorylation . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| We showed that NPM / ALK stimulated cell proliferation and that PI 3K / AKT pathway played an important role in this effect . p27Kip1 is a member of the CDK family inhibitory proteins regulating the entry into S phase . ^^^ In this study we investigated the role of PI 3K / AKT in NPM / ALK dependent downregulation of p27Kip1 protein . ^^^ The p27Kip1 protein expression before and after LY 294002 , wortmannin , or epoxomicin treatment and phosphorylation status of AKT were measured in parental and NPM / ALK+ cells by Western analysis . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| By inhibiting AKT and human kinase interacting stathmin ( hKIS ) , trastuzumab blocks Thr 157 , Thr 198 and Ser 10 induced p27Kip1 translocation from the nucleus to the cytosol , which increases the inhibitory effect of p27Kip1 . ^^^ |
|
| Interacting proteins: P46527 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: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Constitutively active FOXO 4 inhibits Akt activity , regulates p 27 Kip1 stability , and suppresses HER 2 mediated tumorigenicity . ^^^ Given the fact that FOXO 4 mediates p 27 transcription , we hypothesize that an Akt phosphorylation mutant of FOXO 4 ( FOXO4A3 ) , which maintains the activity to transactivate p 27 Kip1 , may be used as an anticancer agent for HER 2 overexpressing cancers . ^^^ We found that FOXO4A3 inhibited the kinase activity of protein kinase B / Akt and reversed HER 2 mediated p 27 mislocation in the cytoplasm . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| EGF stimulates mesangial cell mitogenesis via PI 3 kinase mediated MAPK dependent and AKT kinase independent manner : involvement of c fos and p27Kip1 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Previously , we demonstrated a mechanosensitive activation of phosphoinositide 3 kinase ( PI 3 K ) / protein kinase B ( Akt ) resulting in p27Kip1 transcriptional downregulation and cell cycle entry of vascular smooth muscle cells ( VSMC ) . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Proteins of cyclin E , threonine phosphorylated Akt ( 1 ) at 308 site ( Thr ( 308 ) ) and p 27 ( kip 1 ) were analyzed by Western blotting studies . ^^^ Threonine phosphorylated Akt ( 1 ) protein at 308 site stimulated by TNF alpha was reduced by LXA ( 4 . ) TNF alpha induced decrement in expression of p 27 ( kip 1 ) protein was ameliorated by LXA ( 4 ) in a dose dependent manner . ^^^ CONCLUSION : TNF alpha induced proliferation and increment of cyclin E of rat mesangial cells can be inhibited by LXA ( 4 ) , and these inhibitory effects might be through the mechanisms of STAT ( 3 ) and Akt ( 1 ) / p27 ( kip 1 ) pathway dependent signal transduction . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| While human p 27 could also be mislocalized via the phosphatidylinositol 3 kinase / Akt pathway , only Ral GEF activation was effective for murine p 27 , which lacks the Thr 157 Akt phosphorylation site of human p 27 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Complex regulation of the cyclin dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K / AKT pathway : regulation of p27kip1 expression and localization . ^^^ Here we demonstrate that dysregulation of the PI3K / AKT pathway is important in thyroid carcinogenesis and that p 27 ( kip 1 ) is a key target of the growth regulatory activity exerted by this pathway in thyroid cancer cells . ^^^ Using specific PI3K inhibitors ( LY 294002 , wortmannin , and PTEN ) and a dominant active AKT construct ( myrAKT ) , we demonstrated that the PI3K / AKT pathway controlled thyroid cell proliferation by regulating the expression and subcellular localization of p 27 . ^^^ Results obtained with phospho specific antibodies and with transfection of nonphosphorylable p 27 ( kip 1 ) mutant constructs demonstrated that PI3K / AKT dependent regulation of p 27 ( kip 1 ) mislocalization in thyroid cancer cells occurred via phosphorylation of p 27 ( kip 1 ) at T 157 and T 198 ( but not at S 10 or T 187 ) . ^^^ Analysis of 100 thyroid carcinomas indicated that p 27 ( kip 1 ) phosphorylation at T157 / T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K / AKT pathway . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| In concordance , significant increases in the levels of phosphorylation of total Akt substrates , including : GSK3beta ( Ser 9 ) , tau ( Ser 214 ) , mTOR ( Ser 2448 ) , and decreased levels of the Akt target , p 27 ( kip 1 ) , were found in AD temporal cortex compared with controls . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| These data suggest that activation of cyclin D 1 , MDM 2 , and AKT as well as increased expression and cytoplasmic localization of p27Kip1 may play a role in this model of environmental pollutant induced mammary tumorigenesis . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cyclin D 1 , p21Waf1 , and p27Kip1 expression and phosphorylation of PDGF beta receptor , extracellular signal regulated kinase , and Akt were examined by Western blotting . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| CTGF induced HLF proliferation ; enhanced the expression of cyclin D 1 ; phosphorylated extracellular signal regulated kinase ( ERK ) 1 / 2 , phosphoinositide 3 kinase ( PI 3 K ) , protein kinase B ( PKB ) , and DNA binding activity of signal transducers and activators of transcription 3 ( STAT 3 ) ; and inhibited expression of p 27 ( kip 1 ) . ^^^ These results demonstrate that CTGF induces proliferation of HLF via upregulation of PI 3 K / PKB , STAT 3 , and cyclin D 1 , and downregulation of p 27 ( kip 1 ) . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Following this , apoptosis and the levels of p 21 ( WAF 1 ) , p 27 ( KIP 1 ) , AKT , c Raf , and Her 2 , as well as of the key regulators of apoptosis were determined . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cellular PTEN has been shown to regulate Akt phosphorylation , mitogen activated protein kinase ( MAPK ) phosphorylation , p 27 ( kip 1 ) , and cyclin D 1 protein levels . ^^^ We found that cytoplasmic PTEN down regulates phosphorylation of Akt and up regulates p 27 ( kip 1 ) , whereas nuclear PTEN down regulates cyclin D 1 and prevents the phosphorylation of MAPK . ^^^ |
|
| Interacting proteins: P46527 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 . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| PI3K / Akt signaling regulates p 27 ( kip 1 ) expression via Skp 2 in PC 3 and DU 145 prostate cancer cells , but is not a major factor in p 27 ( kip 1 ) regulation in LNCaP and PC 346 cells . ^^^ BACKGROUND : We compared the involvement of PI3K / PTEN / Akt signaling in the regulation of the cell cycle regulator p 27 ( kip 1 ) and investigated the mechanism of PI3K / PTEN / Akt modulation of p 27 ( kip 1 ) in the prostate cancer cell lines LNCaP , PC 346 , PC 3 , and DU 145 . ^^^ The effects on PI3K / Akt downstream effectors and p 27 ( kip 1 ) expression were monitored on RNA and protein levels . ^^^ RESULTS : PI3K / Akt inhibition in LNCaP and PC 346 cells hardly affected p 27 ( kip 1 ) expression . ^^^ As shown in LNCaP cells , p 27 ( kip 1 ) expression inversely correlated with Skp 2 expression , but Skp 2 was not regulated by Akt . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| U 87 cells in which p 27 had been eliminated by RNA interference exhibited lower Akt levels , shorter Akt turnover , and markedly impaired tumorigenicity in vivo . ^^^ Expression of cytosolic p 27 in primary human breast carcinomas correlated linearly with Akt content as measured by immunohistochemistry . ^^^ These data suggest that cytoplasmic p 27 can exert oncogenic functions by modulating Akt stability , cell survival , and tumorigenicity . . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Ganglioside GM 3 modulates tumor suppressor PTEN mediated cell cycle progression transcriptional induction of p 21 ( WAF 1 ) and p 27 ( kip 1 ) by inhibition of PI 3K / AKT pathway . ^^^ Additionally , ganglioside GM 3 enhances expression of CKI p 27 ( kip 1 ) through the PTEN mediated inhibition of the PI 3K / AKT signaling . ^^^ On the contrary , suppression of PTEN levels by RNA interference restores the enhanced expression of p 53 dependent p 21 ( WAF 1 ) and p 53 independent p 27 ( kip 1 ) through inactivating the effect of PTEN on PI 3K / AKT signaling modulated by ganglioside GM 3 . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The presence of p Akt was accompanied by the phosphorylation of p 27 ( kip 1 ) , FRKHL 1 , MDM 2 , Bad , mTOR , and p70S6K . ^^^ Inhibition of the PI3K / Akt pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt , p 27 ( kip 1 ) , FRKHL 1 , MDM 2 , Bad , mTOR , GSK 3beta , IkappaB , and led to cell cycle arrest and apoptosis . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Expression of the apoptotic related proteins , Bax and p27kip1 , as well as phosphorylated forms of ERK and Akt proteins was assessed by Western blot analysis . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Serum and EGF induced stimulation of cell proliferation and Akt phosphorylation were also significantly reduced by SrcDN , whereas p 27 ( Kip 1 ) expression was increased . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Analyses of expression of downstream mediators phospho AKT ( p AKT ) and p 27 ( KIP 1 ) , in various types of lesions , however , revealed a complex picture . ^^^ Although PIN lesions displayed relatively strong expression of p AKT and p 27 ( KIP 1 ) , there was a notable heterogeneity with variable decrease in their immunostaining in adenocarcinomas . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Negative cell cycle regulator 14 3 3sigma stabilizes p 27 Kip1 by inhibiting the activity of PKB / Akt . ^^^ Protein kinase B / Akt is a crucial regulator of oncogenic signal and can phosphorylate p 27 ( Kip 1 ) to enhance p 27 ( Kip 1 ) degradation , thereby promoting cell growth . ^^^ Here , we show that 14 3 3sigma mediated cell cycle arrest concurred with p 27 ( Kip 1 ) upregulation and Akt inactivation . ^^^ We show that 14 3 3sigma blocks Akt mediated acceleration of p 27 ( Kip 1 ) turnover rate . 14 3 3sigma inhibits Akt mediated p 27 ( Kip 1 ) phosphorylation that targets p 27 ( Kip 1 ) for nuclear export and degradation . 14 3 3sigma inhibits cell survival and tumorigenicity of Akt activating breast cancer cell . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition cell proliferation through the Akt / p27kip1 pathway . ^^^ The lower oxidative stress resulting from the decrease in cellular O2 * delayed the cell cycle at G 1 and significantly slowed SPC A 1 cell growth in association with the dephosphorylation of the serine threonine protein kinase Akt and expression of p27kip1 . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Phosphorylated phosphoinositide 3 kinase ( PI 3 K ) , Akt 1 and p 27 ( kip 1 ) in glomeruli were analyzed by Western Blot . ^^^ The enhanced proteinuria , score of mesangial proliferation , glomerular PCNA positive cells , activities of phosphorylated PI 3 K , Akt 1 and STAT 3 , and reduced p 27 ( kip 1 ) expression were found on day 4 after nephritis induction . 15 Methyl LXA 4 treatment significantly reduced the proteinuria , glomerular infiltration of leukocyte , expressions of IL 1beta and IL 6 protein and mRNA , score of mesangial proliferation , glomerular PCNA positive cells , activities of phosphorylated PI 3 K , Akt 1 , NF kappaB and STAT 3 , and increased the p 27 ( kip 1 ) expression . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| Addition of the PI 3 kinase inhibitor LY 294002 abrogated this response ; moreover , addition of the Akt / PKB inhibitor interleukin ( IL ) 6 hydroxymethyl chiro inositol 2 ( R ) 2 methyl 3 O octadecylcarbonate prevented p 27 ( Kip 1 ) phosphorylation in response to CTGF . ^^^ Further investigation of other Akt / PKB sites on p 27 ( Kip 1 ) , revealed that phosphorylation on threonine 157 was necessary for CTGF mediated p 27 ( Kip 1 ) cytoplasmic localization ; mutation of the threonine 157 site prevented cytoplasmic localization , protected against actin disassembly and inhibited cell migration . ^^^ |
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| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| The hypertrophic effects are at least in part mediated via protein kinase B activation or cyclin dependent kinase inhibitor , p 27 ( kip 1 ) protein expression level in vascular smooth muscle , and renal proximal tubular cells . ^^^ |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46527 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|