| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.5890619 |
| The amino acid residue serine 343 of ILK within the activation loop is required for kinase activity as well as for its interaction with PKB / Akt . 0.5890619^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) , phosphoinositide dependent kinase ( PDK 1 ) , and PKB are implicated in the MMP 2 increase . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Two cellular targets of ILK 1 , glycogen synthase kinase 3 beta ( GSK3beta ) and protein kinase B ( PKB ) / AKT , were differentially affected by ILKAP mediated inhibition of ILK 1 . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Expression of the PI3K pathway members ( p 85 PI3K , FAK , ILK 1 , Akt , and PLC gamma ) was downregulated and expression of the PI3K antagonist PTEN was increased . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We also demonstrate here that ILK is an upstream effector of the Pi ( 3 ) K dependent regulation of both protein kinase B ( PKB / AKT ) and glycogen synthase kinase 3 ( GSK 3 ) . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| The resulting product , PtdIns ( 3 , 4 , 5 ) P 3 , targets Akt / protein kinase B ( PKB ) , Bruton ' s tyrosine kinase ( Btk ) , phosphoinositide dependent kinases ( PDK ) , integrin linked kinase ( ILK ) , atypical protein kinases C ( PKC ) , phospholipase Cgamma and more . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK activates protein kinase B and inhibits the glycogen synthase kinase 3 ( GSK 3 ) activity in a phosphatidylinositol 3 kinase ( PI 3 kinase ) dependent manner . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK phosphorylates downstream targets such as protein kinase B ( PKB , also known as Akt ) and glycogen synthase kinase 3 ( GSK 3 ) and regulates their activities . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| The anti apoptotic effect of PI3K is realized by activation of proteins from another signaling pathway protein kinase B ( PKB ) and / or PKB dependent enzymes ( GSK 3 , ILK ) . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition of integrin linked kinase ( ILK ) suppresses activation of protein kinase B / Akt and induces cell cycle arrest and apoptosis of PTEN mutant prostate cancer cells . ^^^ We recently have demonstrated that the integrin linked kinase ( ILK ) can phosphorylate PKB / Akt on Ser 473 in a phosphoinositide phospholipid dependent manner . ^^^ Transfection of a kinase deficient , dominant negative form of ILK or exposure to a small molecule ILK inhibitor suppresses the constitutive phosphorylation of PKB / Akt on Ser 473 , but not on Thr 308 , in the PTEN mutant prostate carcinoma cell lines PC 3 and LNCaP . ^^^ Transfection of dominant negative ILK and WT PTEN into these cells also results in the inhibition of PKB / Akt kinase activity . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) is an integrin interacting protein kinase which has been identified as a potential PDK 2 , as it is capable of phosphorylating PKB / Akt on Ser 473 , and stimulating its activity . ^^^ This effect is reversible by the transfection and expression of a dominant negative , kinase deficient ILK ( ILK KD ) , as well as by a dominant negative PKB / Akt ( PKB AAA ) . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK also phosphorylates protein kinase B ( PKB / Akt ) and stimulates its activity . ^^^ We have shown that ILK is an upstream effector of the phosphatidylinositol 3 kinase dependent regulation of PKB / Akt . ^^^ ILK has been shown to phosphorylate PKB / Akt on Ser 473 in vitro and in vivo . ^^^ A small molecule ILK inhibitor suppresses the phosphorylation of PKB at the Ser 473 but not the Thr 308 site in the PTEN mutant cells . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) was identified by its interaction with the cytoplasmic tail of human beta 1 integrin and previous data suggest that ILK is a component of diverse signaling pathways , including integrin , Wnt , and protein kinase B . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Overexpression of ILK stimulated NF kappaB activity and inhibition of ILK or protein kinase B ( PKB / Akt ) suppressed this activation . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Other factors acting on Akt such as ILK activation and decreased PTEN phosphatase activity appear to be involved at the conversion stage . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| In this study we have examined the interactions of PKB , PDK 1 , and ILK in resting and stimulated platelets . ^^^ We demonstrate that in platelets PKB is physically associated with PDK 1 and ILK . ^^^ It would therefore appear that formation of a tertiary complex between PDK 1 , ILK , and PKB may be necessary for phosphorylation of PKB . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| This effect of SAP 1 was dependent on cellular caspase activities and was preceded by inactivation of two serine threonine protein kinases , Akt and integrin linked kinase ( ILK ) , both of which function downstream of phosphoinositide ( PI ) 3 kinase to promote cell survival . ^^^ Coexpression of constitutively active forms of PI 3 kinase or Akt ( which fully restored Akt and ILK activities ) resulted in partial inhibition of SAP 1 induced cell death . ^^^ Furthermore , expression of a dominant negative mutant of PI 3 kinase did not induce cell death as efficiently as did SAP 1 , although this mutant inhibited Akt and ILK activities more effectively than did SAP 1 . ^^^ These results suggest that SAP 1 induces apoptotic cell death by at least two distinct mechanisms : inhibition of cell survival signaling mediated by PI 3 kinase , Akt , and ILK and activation of a caspase dependent proapoptotic pathway . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Identification of a plasma membrane Raft associated PKB Ser 473 kinase activity that is distinct from ILK and PDK 1 . ^^^ Two major phosphoproteins and integrin linked kinase ( ILK ) were detected in partially purified PKB Ser 473 kinase preparations . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| In this study , we found that in A 549 and HEK 293 cells non selective PKC inhibitors Ro 31 8220 and bisindolylmaleimide 8 , and PKCbeta inhibitor LY 379196 , caused Akt / PKB phosphorylation at Ser 473 and increased the upstream activator , integrin linked kinase ( ILK ) activity . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We show herein that PPARbeta modulates Akt 1 activation via transcriptional upregulation of ILK and PDK 1 , revealing a mechanism for the control of Akt 1 signaling . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Moreover , whereas Br C 4 nearly abolished insulin stimulated integrin linked kinase ( ILK ) activity , it only inhibited insulin stimulated PKB activity by 20 % , implying that ILK was not the major kinase for Ser ( 473 / 474 ) phosphorylation . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We report that integrin signaling prevents apoptosis of embryonic hippocampal neurons by a mechanism involving integrin linked kinase ( ILK ) that activates Akt kinase . ^^^ Instead , we show a requirement for ILK in integrin receptor induced Akt activation . ^^^ ILK was activated following integrin stimulation and dominant negative ILK blocked integrin mediated Akt activation and cell survival . ^^^ Activation of ILK and Akt were also required for neuroprotection by substrate associated laminin . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| NGF mediated stimulation of phosphorylation of both AKT and the Tau kinase glycogen synthase kinase 3 ( GSK 3 ) was inhibited in the presence of KP 392 and after overexpression of ILK DN . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK can mediate the phosphorylation of a variety of intracellular substrates , most notable of which are : protein kinase B ( PKB / Akt ) , glycogen synthase kinase 3 ( GSK 3 ) and myosin light chain . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| PTF induced up regulation of ILK expression in ovarian cancer cell lines correlated with the activation of the downstream protein kinase B ( PKB / Akt ) pathway . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Known targets of ILK , PKB / Akt or glycogen synthase kinase 3beta are not obviously involved in ILK induced L 6 differentiation . ^^^ Insulin stimulated phosphorylation of PKB at Ser 473 is unimpaired in the ILK ( E359K ) cells , suggesting that PKB is not a myogenic target of ILK . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Third , PINCH 1 and ILK are required for optimal activating phosphorylation of PKB / Akt , an important signaling intermediate of the survival pathway . ^^^ Whereas depletion of ILK reduced Ser 473 phosphorylation but not Thr 308 phosphorylation of PKB / Akt , depletion of PINCH 1 reduced both the Ser 473 and Thr 308 phosphorylation of PKB / Akt . ^^^ Fourth , PINCH 1 and ILK function in the survival pathway not only upstream but also downstream ( or in parallel ) of protein kinase B ( PKB ) / Akt . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We observed that integrin linked kinase ( ILK ) was also up regulated by TGF beta 1 in good accordance with PKB Ser 473 phosphorylation . ^^^ We first found that TGF beta 1 could stimulate PKB Ser 473 phosphorylation possibly via up regulating ILK expression . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| VEGF induced phosphorylation of protein kinase B ( PKB / Akt ) , a regulator of cell survival and apoptosis , on serine 473 , but not on threonine 308 , in an ILK dependent manner . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We investigated the role of endogenous cellular ILKAP in antagonizing ILK signaling of two key targets , PKB and GSK3beta . ^^^ Consistent with the silencing data , ILKAP inhibition of ILK selectively inhibited S 9 phosphorylation of GSK3beta without affecting S 473 phosphorylation of PKB . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Stable expression of ILK KD in HER2 / neu transformed cells suppressed Akt phosphorylation and the expression of IkappaB kinase alpha and beta ( IKKalpha and beta ) at both the protein and mRNA levels , preventing IkappaB alpha degradation and NF kappaB activation . ^^^ Furthermore , HER2 / neu stimulated the transcriptional activity of the putative IKKbeta promoter through ILK and Akt . ^^^ Our results demonstrate that upregulation of IKKalpha and IKKbeta by the ILK / Akt pathway is required for the HER2 / neu mediated NF kappaB antiapoptotic pathway . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We show that Cyr 61 can enhance tumorigenicity of glioma cells acting through activated integrin linked kinase ( ILK ) to stimulate beta catenin TCF / Lef and Akt signaling pathways . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| TGFbeta mediated phosphorylation of Akt at Ser 473 was inhibited by dominant negative ILK and PI3K inhibitors , LY 294002 and wortmannin . ^^^ Treatment with TGFbeta stimulated induction of Akt and ILK kinase activity in HaCat control cells . ^^^ In addition , PI3K inhibitor , dominant negative Akt , and dominant negative ILK could not block TGFbeta mediated C terminal phosphorylation of Smad 2 . ^^^ Taken together , these data suggest that PI3K ILK Akt pathway that is independent of the TGFbeta induced Smad pathway is required for TGFbeta mediated epithelial to mesenchymal transition . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Loss of PINCH 1 or ILK , to which alpha and beta parvin bind , significantly reduced the activation of Rac , a key signaling event that controls lamellipodium formation and cell spreading . ^^^ Overexpression of beta parvin , however , was insufficient for stimulation of Rac activation or lamellipodium formation , although it was sufficient for promotion of apoptosis , another important cellular process that is regulated by PINCH 1 , ILK , and alpha parvin . ^^^ These results identify Rac as a downstream target of PINCH 1 , ILK , and parvin . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| This promoter was activated in cell lines in response to agents that induce Snail transcription and the mesenchymal phenotype , as addition of the phorbol ester PMA or overexpression of integrin linked kinase ( ILK ) or oncogenes such as Ha ras or 5 Akt . ^^^ Although other regions of the promoter were required for a complete stimulation by Akt or ILK , a minimal fragment ( 78 / +59 ) was sufficient to maintain the mesenchymal specificity . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) , bound to the cytoplasmic tails of integrin beta 1 , beta 2 , and beta 3 , is thought to signal through AKT and glycogen synthase kinase 3beta ( GSK 3beta ) for survival and proliferation regulation . ^^^ AKT , GSK 3beta cyclin D 1 , mitogen activated protein kinase kinase 1 / 2 mitogen activated protein kinase , and c Jun NH 2 terminal kinase signaling was dysregulated in irradiated ILK hk mutants . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| There was also reduced phosphorylation of the ILK kinase substrate , Akt . ^^^ However , phenotypic rescue of ILK deficient EC by wild type ILK , but not by a constitutively active mutant of Akt , suggests regulation of EC survival by ILK in an Akt independent manner . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| EGF induced phosphorylation of two ILK targets , PKB ( Ser 473 ) and glycogen synthase kinase 3beta ( Ser 9 ) , was also inhibited by ParvB . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We administered the PI 3 K inhibitor , LY 294002 , into mouse brains after tFCI and examined the role of PI 3 K in the ILK pathway and expression of the ILK / Akt complex by immunohistochemistry , Western blot analysis , and coimmunoprecipitation . ^^^ Coimmunoprecipitation revealed that the direct reaction of ILK / Akt transiently increased concurrent with the increase in ILK after tFCI . ^^^ Moreover , the ILK / Akt complex was prevented by LY 294002 , but promoted by SOD 1 . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| We found that thymosin beta 4 formed a functional complex with PINCH and integrin linked kinase ( ILK ) , resulting in activation of the survival kinase Akt ( also known as protein kinase B ) . ^^^ After coronary artery ligation in mice , thymosin beta 4 treatment resulted in upregulation of ILK and Akt activity in the heart , enhanced early myocyte survival and improved cardiac function . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Hepatocytes that had been given a different treatment were stained for caspase 3 ( apoptosis marker ) and phospho Akt Ser 473 ( survival marker ) and were measured for their integrin linked kinase ( ILK ) activity . ^^^ RESULTS : Ligation of integrins using antibodies against the beta 1 integrin chain or RGD peptides protected isolated hepatocytes from apoptosis and resulted in an increased ILK activity and persistent phosphorylation of protein kinase B / Akt at serine 473 . ^^^ CONCLUSIONS : Integrin activation in isolated hepatocytes contributes to the activation of ILK , phosphorylation of Akt on serine residue 473 , and inhibition of apoptosis . ^^^ Integrin signaling through the ILK phospho Akt pathway protects isolated hepatocytes from apoptosis . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Overexpression of ILK leads to altered expression of cell cycle regulators , a decreased level of cell adhesion to the extracellular matrix , a decreased level of apoptosis , in vitro phosphorylation of Akt , and tumor formation in nude mice . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) couples integrins and growth factors to downstream signaling pathways involving phosphatidylinositol 3 kinase , protein kinase B / Akt ( PKB / Akt ) , and glycogen synthase kinase 3beta . ^^^ 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 . ^^^ However , we did not observe an effect on phosphoinositide dependent kinase 1 , glycogen synthase kinase 3beta , and extracellular signal regulated kinase phosphorylation or on total PKB and ILK protein expression levels with QLT 0254 treatment . ^^^ These results show in vivo evidence that ILK plays a prominent role in oncogenic phosphatidylinositol 3 kinase / PKB signaling in vivo with major impact on the mammalian target of rapamycin , signal transducers and activators of transcription 3 , and forkhead in rhadomyosarcoma signaling pathways , suggesting that ILK inhibitors might show activity in pancreatic cancer patients . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK mediates actin filament rearrangements and cell migration and invasion through PI3K / Akt / Rac1 signaling . ^^^ Overexpression of dominant negative mutants of Akt inhibited ILK dependent activation of p70S6K1 , indicating that Akt is upstream of p70S6K1 in response to ILK signaling . ^^^ Inhibition of Akt , Rac 1 , or p70S6K1 inhibited the effects of ILK on actin filaments and cell migration , suggesting a regulatory role of the PI3K / Akt / p70S6K1 / Rac1 signaling pathway in response to ILK signaling . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ILK in PTEN mutant human glioblastomas inhibits PKB / Akt activation , induces apoptosis , and delays tumor growth . ^^^ Integrin linked kinase ( ILK ) has been shown to regulate PKB / Akt activity with the loss of PTEN in prostate cancer . ^^^ We now demonstrate that ILK activity regulates PKB / Akt activity in glioblastoma cells . ^^^ Transfection of ILK antisense ( ILKAS ) or exposure to a small molecule ILK inhibitor suppresses the constitutive phosphorylation of PKB / Akt on Ser 473 in PTEN mutant glioblastoma cell lines . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B / Akt . ^^^ We also examined the effects of modulating ILK expression on gemcitabine induced caspase 3 mediated apoptosis , phosphorylation status of Akt ( Ser 473 ) and glycogen synthase kinase . ^^^ ILK knockdown attenuated Akt Ser 473 and glycogen synthase kinase phosphorylation , whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| In the present study , we demonstrate that integrin linked kinase ( ILK ) , which is a focal adhesion protein activated by both ECM and growth factors , is required for the activation of Rac and Cdc 42 in epithelial cells . ^^^ The use of ILK siRNA or small molecule inhibitors to inhibit ILK expression and kinase activity , respectively , results in diminished cell spreading and actin cytoskeleton reorganization , concomitant with a reduction in Rac and Cdc 42 activation . ^^^ Studies into the mechanism of ILK mediated Rac activation suggest an important role for the ILK beta parvin interaction and the activity of the Rac / Cdc42 specific guanine nucleotide exchange factor alpha PIX downstream of ILK . ^^^ Taken together , these data demonstrate an essential role of ILK kinase activity in Rac and Cdc 42 mediated actin cytoskeleton reorganization in epithelial cells , further solidifying a role for ILK in the regulation of cancer cell motility and invasiveness . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Integrin linked kinase ( ILK ) is associated with the beta 1 integrin in the focal adhesion complex and as such is a candidate kinase that may regulate Akt phosphorylation and fibroblast viability . ^^^ Here , we show that ILK activity decreased in response to collagen matrix contraction , which correlated with Akt dephosphorylation and induction of fibroblast apoptosis . ^^^ In contrast , enforced activation of beta 1 integrin by activating antibody preserved ILK and Akt activity during collagen matrix contraction , and this is associated with protection from collagen contraction induced apoptosis . ^^^ Knock down of ILK by small , interfering RNA ( siRNA ) attenuated Akt phosphorylation in response to ligation of beta 1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction . ^^^ Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis , whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Treating thyroid cancer cell lines with a new ILK inhibitor , QLT 0267 , inhibited epidermal growth factor induced phosphorylation of AKT , inhibited cell growth , and induced apoptosis in the NPA 187 , DRO , and K 4 cell lines . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Then we studied the changes of FAK , ILK , beta catenin , and PKB in this apoptotic model by Western blot . ^^^ RESULTS : We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC 7721 hepatocellular carcinoma cell and the apoptosis of SMMC 7721 cell was preceded by the loss or decrease of FAK , ILK , PKB , and beta catenin or the damage of cell matrix and cell cell adhesion . ^^^ CONCLUSION : Our results suggested that the decrease of adhesion signal molecules , FAK , ILK , PKB , and beta catenin , could induce hepatocellular carcinoma cell apoptosis . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cytoplasmic / membrane levels of protein kinase B ( Akt ) , a target of ILK , and its phosphorylated active form were decreased in treated female rats . ^^^ Both ILK and Akt can phosphorylate glycogen synthetase kinase 3beta ( GSK3beta ) , rendering it inactive . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| However , the association of PKB with integrin linked kinase ( ILK ) , a kinase that potentially phosphorylates PKB at Ser 473 , and ILK abundance were similar in both age groups . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Double stranded DNA dependent protein kinase ( DNA PK ) , ataxia telangiectasia mutated ( ATM ) gene product , integrin linked kinase ( ILK ) , protein kinase Calpha ( PKCalpha ) , and mammalian target of rapamycin ( mTOR ) , when complexed to rapamycin insensitive companion of mTOR ( RICTOR ) , have all been identified as playing a critical role in Akt Ser 473 phosphorylation . ^^^ In contrast , immunopurified low density microsome vesicles containing ILK could not phosphorylate Akt on Ser 473 in vitro . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| A possible candidate is integrin linked kinase ( ILK ) , which has been shown to phosphorylate Akt at Ser 473 in vitro . ^^^ We found that a newly developed small molecule compound ( QLT 0267 ) effectively inhibited signaling through the ILK / Akt cascade in glioma cells by blocking the phosphorylation of Akt and downstream targets , including mammalian target of rapamycin and glycogen synthase kinase 3beta . ^^^ Thus , blocking the ILK / Akt pathway is a potential strategy for molecular targeted therapy for gliomas . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK over expression in human colon cancer progression correlates with activation of beta catenin , down regulation of E cadherin and activation of the Akt FKHR pathway . ^^^ We studied , by immunohistochemistry , ILK , beta catenin , E cadherin , p Akt and p FKHR protein expression in 125 primary colon carcinomas and 45 corresponding lymph node metastases . ^^^ Activation of beta catenin , down regulation of E cadherin and activation of the Akt FKHR pathway correlated significantly with both ILK expression and tumour progression parameters . ^^^ In conclusion , our results suggest that ILK may have an important role in progression of human colon cancer , possibly through in vivo regulation of beta catenin , E cadherin and Akt pathways . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Signaling studies in ILK deficient T cells demonstrated diminished phosphorylation of Akt on the activating phosphorylation site , Ser 473 , and a concordant decrease in Akt kinase activity following stimulation with the chemokine SDF 1 . ^^^ These data extend the role of ILK to immune cell trafficking and survival via modulation of Akt and Rac dependent substrates , and have implications for cell recruitment in both homeostatic and pathological processes . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Increased ILK expression correlated with the activation of PKB / Akt , the phosphorylation of GSK 3beta , and the increased expression of cyclin E and cdk 2 kinase . ^^^ ILK small interfering RNA inhibited Akt phosphorylation and reduced pro MMP 2 / 9 activities but had no effect on Erk activation or cell morphology . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here , we show that integrin linked kinase ( ILK ) , which is either activated or overexpressed in many types of cancers , is a critical regulator of breast cancer cell survival through the protein kinase B ( PKB ) / Akt pathway but is largely dispensable for the survival of normal breast epithelial cells and mesenchymal cells . ^^^ We show that inhibition of ILK activity with a pharmacologic ILK inhibitor , QLT 0267 , results in the inhibition of PKB / Akt Ser 473 phosphorylation , stimulation of apoptosis , and a decrease in mammalian target of rapamycin ( mTOR ) expression in human breast cancer cells . ^^^ The inhibition of PKB / Akt Ser 473 phosphorylation by QLT 0267 in breast cancer cells was rescued by a kinase active ILK mutant but not by a kinase dead ILK mutant . ^^^ Our data point to an `` ILK addiction ' ' of breast cancer cells whereby they become dependent on ILK for cell survival through the mTOR PKB / Akt signaling pathway and show that ILK is a promising target for the treatment of breast cancer . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Glioblastoma cells transfected with ILKAS exhibited reduced levels of ILK and phosphorylated PKB / Akt on Ser 473 but not PKB / Akt on Thr 308 as shown by immunoblot analysis . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| An ILK small molecule inhibitor ( KP 392 ) or transfection with a dominant negative ILK mutant effectively blocks the phosphorylation of downstream signals , Akt and glycogen synthase kinase 3beta . ^^^ In ovarian carcinoma xenografts , ABT 627 , a specific ET ( A ) R antagonist , suppresses ILK expression , Akt and glycogen synthase kinase 3beta phosphorylation , and tumor growth . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| This is concomitant with the activation of the integrin linked kinase ( ILK ) pathway , leading to the activation and nuclear translocation of Akt and the inactivation of glycogen synthase kinase 3beta ( GSK3beta ) . ^^^ Overall , these data indicate that Cx 32 is downregulated by the ILK pathway activation in rat hepatocytes and that this is mediated via the activation and nuclear translocation of Akt . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| ILK GFP F enhances cell spreading on fibronectin and induces a constitutive increase in the levels of GTP bound Rac 1 . ^^^ Conversely , ILK knock down by siRNA transfection decreases active Rac 1 . ^^^ Endogenous ILK was found to associate with PKL ( paxillin kinase linker ) and the Rac / Cdc42 guanine nucleotide exchange factor betaPIX . ^^^ Further , expression of a dominant negative betaPIX mutant reversed the increase in active Rac 1 levels of ILK GFP F expressing cells , thus placing betaPIX in the pathway leading from ILK to Rac 1 activation . ^^^ However , expression of constitutively active Rac only partially restores the spreading defects of ILK depleted cells , suggesting that an additional ILK dependent signal is required for cell spreading . . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Complementary experiments using a constitutively active form of Akt 1 revealed that the observed protective effect of ILK inhibition is dependent on the associated downregulation of virus induced Akt activation . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Accordingly , in msq mutant embryos , heart failure can be suppressed by expression of ILK , and also of a constitutively active form of Protein Kinase B ( PKB ) , and VEGF . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Our studies also showed that ILK is involved in the phosphorylation of ERK 1 / 2 , p 38 MAPK , JNK , and PKB and that selective inhibition of ILK expression by siRNA results in a significant decrease in their phosphorylation . ^^^ |
|
| Interacting proteins: Q13418 and P31749 |
Pubmed |
SVM Score :0.0 |
| Importantly , the loss of ILK is accompanied by a reduction in cardiac Akt phosphorylation , which normally provides a protective response against stress . ^^^ |
|