Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.64869147
Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH 2 domain mediated association of the GRB 2 adaptor protein and the c Src protein tyrosine kinase ( PTK ) with FAK in vivo , and also results in activation of mitogen activated protein kinase ( MAPK ) . 0.64869147^^^ The GRB 2 SH2 domain binds directly to tyrosine phosphorylated FAK . 0.57500466^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.77693892
Finally , we demonstrated that HGF stimulates the association of FAK with Grb 2 in vitro and in intact cells and provided evidence that FAK might contribute to the activation of mitogen activated protein kinase through Ras in HGF signaling by functioning as an adapter molecule . . 0.77693892^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.52034554
FAK associates with several different signaling proteins such as Src family PTKs , p130Cas , Shc , Grb 2 , PI 3 kinase , and paxillin . 0.52034554^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.62477517
FAK in MRL lpr glomeruli is highly tyrosine phosphorylated and is associated with adapter protein Grb 2 . 0.62477517^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.66953713
Finally , we provide evidence that the Src dependent association of FAK with Grb 2 and p 130 ( Cas ) are both required for the regulation of cell cycle progression by FAK . 0.66953713^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.83206385
FAK was constitutively associated with the adapter protein Grb 2 in HER 14 cells . 0.83206385^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.51348272
In the present studies using human monocytes , we show that M CSF induces interaction of the Grb 2 adaptor protein with the focal adhesion kinase pp125FAK . 0.51348272^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
These data suggest that RAFTK is a novel member of the FAK family , that it localizes to focal adhesion like structures in CMK megakaryocytic cells , that it participates in integrinmediated signaling pathways in megakaryocytes , and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb 2 via SH 2 phosphotyrosine interactions . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
We showed previously that the c Src nonreceptor PTK and the Grb 2 SH2 / SH3 adaptor protein bound directly to FAK after fibronectin stimulation ( D . ^^^ Here , we present evidence that c Src association with FAK is required for Grb 2 binding to FAK . ^^^ Using a tryptic phosphopeptide mapping approach , the in vivo phosphorylation of the Grb 2 binding site on FAK ( Tyr 925 ) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in 5 Src transformed NIH 3T3 cells . ^^^ Using epitope tagged FAK constructs , transiently expressed in human 293 cells , we determined the effect of site directed mutations on c Src and Grb 2 binding to FAK . ^^^ Mutation of FAK Tyr 925 disrupted Grb 2 binding , whereas mutation of the c Src binding site on FAK ( Tyr 397 ) disrupted both c Src and Grb 2 binding to FAK in vivo . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Previously identified Src sites include catalytic domain tyrosines 576 and 577 , important for maximal FAK kinase activity , and tyrosine 925 , which permits an SH 2 mediated association with Grb 2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
FAK autophosphorylation at Tyr 397 promotes Src homology 2 ( SH 2 ) domain binding of Src family PTKs , and c Src phosphorylation of FAK at Tyr 925 creates an SH 2 binding site for the Grb 2 SH2 SH 3 adaptor protein . ^^^ FN stimulated Grb 2 binding to FAK may facilitate intracellular signaling to targets such as ERK 2 mitogen activated protein kinase . ^^^ Tyr ) and Grb 2 binding to FAK were reduced , whereas the tyrosine phosphorylation of another signaling protein , p130cas , was not detected in the Src cells . ^^^ Stable expression of residues 1 to 298 of Src ( Src 1 298 , which encompass the SH 3 and SH 2 domains of c Src ) in the Src cells blocked Grb 2 binding to FAK ; but surprisingly , Src 1 298 expression also resulted in elevated p130cas P . ^^^ These results show that there are additional FN stimulated pathways to ERK 2 that do not involve Grb 2 binding to FAK . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Focal adhesion kinase ( FAK ) associates with integrin receptors , and FN stimulated phosphorylation of FAK at Tyr 397 and Tyr 925 promotes the binding of Src family PTKs and Grb 2 , respectively . ^^^ To investigate the mechanisms by which FAK , c Src , and Grb 2 function in FN stimulated signaling events to ERK 2 , we expressed wild type and mutant forms of FAK in human 293 epithelial cells by transient transfection . ^^^ Expression of the Grb 2 binding site Phe 925 mutant of FAK enhanced activation of ERK 2 , whereas a kinase inactive Arg 454 mutant FAK did not . ^^^ Expression of wild type and Phe 925 FAK , but not Phe 397 FAK , enhanced p 130 ( Cas ) association with FAK , Shc tyrosine phosphorylation , and Grb 2 binding to Shc after FN stimulation . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Here it is reported that ET 1 promotes the formation of stress fibers and focal adhesions and the tyrosine phosphorylation of focal adhesion kinase ( FAK ) and paxillin , as well as Src activation and association of phosphorylated FAK with Grb 2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
We found that such a shear stress increased the tyrosine phosphorylation and the kinase activity of focal adhesion kinase ( FAK ) and its association with growth factor receptor binding protein 2 ( Grb 2 ) in a rapid and transient manner , suggesting that FAK may be linked to these mitogen activated protein kinase signaling pathways through a Grb2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Activation and autophosphorylation of FAK lead to its binding to a number of intracellular signaling molecules , including Src , Grb 2 and PI 3 kinase . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Src association with FAK may also lead to its phosphorylation of other sites on FAK , including a binding site for Grb 2 . ^^^ Cell adhesion dependent association of FAK and Grb 2 may provide a mechanism by which MAP kinase is activated in cell adhesion . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
The results indicated that AlFx dose dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin , as well as of the adaptor molecules p46shc , p52shc , and p66shc and their association with GRB 2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
FN stimulation of NIH 3T3 fibroblasts promotes c Src and FAK association in the Triton insoluble cell fraction , and the time course of FN stimulated ERK 2 activation paralleled that of Grb 2 binding to FAK at Tyr 925 and Grb 2 binding to Shc . ^^^ Treatment of fibroblasts with protein kinase C inhibitors or with the PTK inhibitor herbimycin A or PP 1 resulted in reduced Src PTK activity , no Grb 2 binding to FAK , and lowered levels of ERK 2 activation . ^^^ In vitro , FAK directly phosphorylated Shc Tyr 317 to promote Grb 2 binding , and in vivo Grb 2 binding to Shc was observed in herbimycin A treated fibroblasts after FN stimulation . ^^^ Surprisingly , expression of Phe 925 FAK with Phe 317 Shc also did not block signaling to ERK 2 , whereas FN stimulated signaling to ERK 2 was inhibited by coexpression of an SH 3 domain inactivated mutant of Grb 2 . ^^^ Our studies show that FN receptor integrin signaling upstream of Ras and ERK 2 does not follow a linear pathway but that , instead , multiple Grb 2 mediated interactions with Shc , FAK , and perhaps other yet to be determined phosphorylated targets represent parallel signaling pathways that cooperate to promote maximal ERK 2 activation . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Increased Pyk 2 tyrosine phosphorylation paralleled the time course of Grb 2 binding to Shc and activation of ERK 2 in FAK cells . ^^^ Significantly , repression of endogenous Src family PTK activity by p 50 ( csk ) overexpression inhibited FN stimulated cell spreading , Pyk 2 tyrosine phosphorylation , Grb 2 binding to Shc , and ERK 2 activation in the FAK but not in FAK+ cells . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
In pp 125 ( FAK ) expressing cells , this was concomitant with increased association of IRS 1 with Src homology 2 containing proteins such as growth factor receptor bound protein 2 , phosphatidylinositol ( PI ) 3 kinase p85alpha subunit , and Src homology 2 containing protein tyrosine phosphatase 2 . ^^^ In contrast , no change in mitogen activated protein kinase activity was observed , indicating that pp 125 ( FAK ) induced association between IRS 1 and growth factor receptor bound protein 2 does not affect the mitogen activated protein kinase pathway . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
FAK interacts with a number of signaling and cytoskeletal proteins , including Src , phosphatidylinositol 3 kinase , Grb 2 , p130Cas and paxillin . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
In this report , we have examined the role of FAK association with Grb 2 and p 130 ( Cas ) , two downstream events of the FAK / Src complex that could mediate integrin stimulated activation of extracellular signal regulated kinases ( Erks ) . ^^^ We show that a Y925F FAK mutant was able to promote cell migration as efficiently as FAK and that the transfected FAK demonstrated no detectable association with Grb 2 in CHO cells . ^^^ Together , these results demonstrate that p 130 ( Cas ) , but not Grb 2 , is a mediator of FAK promoted cell migration and suggest that FAK / p 130 ( Cas ) complex targets downstream pathways other than Erks in mediating FAK promoted cell migration . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
We found that CSR induced the activation of FAK and Src and the association of FAK and Shc , a signaling molecule linking growth factor receptor tyrosine kinase and Grb 2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Interestingly , cells expressing a FAK mutant defective in Grb 2 binding exhibited a rate of migration approximately 50 % lower than that of cells expressing wild type FAK in response to HGF stimulation . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
In immunoprecipitation studies , Pyk 2 , as well as FAK , seemed to associate with Shc through Grb 2 . ^^^ With the use of glutathione S transferase fusion proteins containing Shc SH 2 , Grb 2 SH2 , and Grb 2 N terminal and C terminal SH 3 domains , it was implied that the proline rich region of Pyk 2 ( and FAK ) binds to the N terminal SH 3 domain of Grb 2 and that the phosphotyrosine residue of Shc binds to the SH 2 domain of Grb 2 . ^^^ Furthermore , Pyk 2 , as well as FAK , might have one or more important roles in post aggregation tyrosine phosphorylation events , in association with the cytoskeleton and through interaction with adapter proteins including Grb 2 and Shc . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Analysis of these cells indicates that FAK is not necessary for efficient tyrosine phosphorylation of Shc , association of Shc with Grb 2 , and activation of ERK in response to matrix adhesion . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
This complex , in addition to beta dystroglycan , was also found to contain Grb 2 and focal adhesion kinase p125FAK ( FAK ) . ^^^ Anti FAK antibodies co immunoprecipitated Grb 2 with FAK . ^^^ We isolated both FAK and Grb 2 from synaptosomal extracts by chromatography on immobilized recombinant beta dystroglycan . ^^^ At the synapses , the adaptor protein Grb 2 may mediate FAK beta dystroglycan interaction , and it may play a role in transferring information between the dystroglycan complex and other signaling pathways . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins GRB 2 , Shc , and nonreceptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Here , we show that hypoxia induced tyrosine phosphorylation of p 125 ( FAK ) and paxillin and that hypoxia induced activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins Shc and GRB 2 , and non receptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
These events were paralleled by c Src activation and binding to Fak and by an association of Grb 2 and p 85 subunit of phosphatidylinositol 3 kinase with Fak . ^^^ Erk1 / 2 and Akt , two possible downstream effectors of Fak via Grb 2 and phosphatidylinositol 3 kinase , were also shown to be activated in parallel with Fak . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Furthermore , we found that FAK kinase activity and the autophosphorylation site ( Tyr 397 ) are important in E . coli invasion of HBMEC , whereas the Grb 2 binding site ( Tyr 925 ) is not required . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Additionally , FAK was linked to the hypertrophic response as follows : 1 ) coimmunoprecipitation of beta1D and FAK was detected ; 2 ) FAK overexpression induced ANF luciferase ; 3 ) rapid and sustained phosphorylation of FAK was induced by alpha ( 1 ) adrenergic stimulation ; and 4 ) blunting of the alpha ( 1 ) adrenergically modulated hypertrophic response was caused by FAK mutants , which alter Grb 2 or Src binding , as well as by FAK related nonkinase , a dominant interfering FAK mutant . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
In the present study , we investigated if these results were related to changes in the mobilization of intracellular calcium , activation of phospholipase D ( PLD ) or amounts of GPIIIa and the intracellular tyrosine kinases Fak , Syk , Grb 2 , Shc and rhoA . ^^^ Levels of Fak , Syk , Shc , Grb 2 and rhoA appeared equal in patients and controls . ^^^ Moreover , no apparent differences in the intracellular amounts of Fak , Syk Shc , Grb 2 and rhoA could be detected between PV and control platelets . . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Co expression studies in human 293T cells showed that 5 Src could associate with and phosphorylate a Phe 397 FAK mutant at Tyr 925 promoting Grb 2 binding to FAK in suspended cells . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Differential regulation of cell migration and cell cycle progression by FAK complexes with Src , PI3K , Grb 7 and Grb 2 in focal contacts . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Increases of diastolic pressure from approximately 0 to approximately 15 mmHg rapidly increased FAK tyrosine phosphorylation ( maximum : 2 . 3 fold ) and binding to c Src ( maximum : 2 . 8 fold ) and Grb 2 ( maximum : 3 . 6 fold ) . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
MATERIALS AND METHODS : ( 1 ) The adhesion of T 24 cells , a fibronectin receptor positive TCC cell line , to fibronectin was investigated ; ( 2 ) the MAPK activation after fibronectin stimulation in bladder cancer cell lines was examined by Western blotting using an antiactive MAPK antibody , and ( 3 ) FAK , Sos , and Grb 2 were also examined by Western blot analysis . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Collagen 4 stimulated Grb 2 binding site FAK Y 925 phosphorylation , which was inhibited by PP 2 and required FAK Y 397 autophosphorylation . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
The focal adhesion targeting ( FAT ) domain of focal adhesion kinase ( FAK ) is critical for recruitment of FAK to focal adhesions and contains tyrosine 926 , which , when phosphorylated , binds the SH 2 domain of Grb 2 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
In addition to interactions with multiple signaling adaptors Grb 2 , SHC , SCK , and NSP 2 , EGF receptors in HN 5 cells were shown to form direct or indirect physical interactions with additional kinases including ACK 1 , focal adhesion kinase ( FAK ) , Pyk 2 , Yes , EphA 2 , and EphB 4 . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Prolidase activity and collagen biosynthesis are supposed to be regulated by beta ( 1 ) integrins , which initiate a signaling pathway in which several kinases and intracellular proteins are involved , including focal adhesion kinase pp 125 ( FAK ) ( FAK ) , Src , Shc , growth factor receptor bound protein 2 ( Grb 2 ) , son of sevenless protein ( SOS ) , Ras , Raf and mitogen activated protein kinases ( MAPK ) , extracellular signal regulated kinase 1 ( ERK ( 1 ) ) and kinase 2 ( ERK ( 2 ) ) . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
PP 2 and RGD peptide also inhibited high pressure induced binding of FAK with the effector Grb 2 and blocked activation of extracellular regulated kinase ( ERK ) 1 / 2 in vessels at 150 mm Hg . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
It involves translocation ( i . e . activation ) of PKCalpha from the cytosol to the membrane and / or the Triton 10 100 insoluble subcellular fractions , with recruitment into a complex with alphaVbeta 3 integrin , growth factor receptor bound protein ( Grb 2 ) , focal adhesion kinase ( FAK ) in CHO cells and proline rich tyrosine kinase ( PYK 2 ) in osteoclasts . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
This appears to occur through assembly of an EphB associated protein complex that includes focal adhesion kinase ( FAK ) , Src , Grb 2 , and paxillin and the subsequent activations of FAK , Src , paxillin , and RhoA . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
Here , we suppressed FAK activity in 4T1 breast carcinoma cells resulting in reduced FAK Y 925 phosphorylation , Grb 2 adaptor protein binding to FAK , and signaling to mitogen activated protein ( MAP ) kinase ( MAPK ) . ^^^ Loss of a FAK Grb 2 MAPK linkage did not affect 4T1 cell proliferation or survival in culture , yet FAK inhibition reduced vascular endothelial growth factor ( VEGF ) expression and resulted in small avascular tumors in mice . ^^^ This FAK Grb 2 MAPK linkage was essential in promoting angiogenesis as reconstitution experiments using Src transformed FAK null fibroblasts revealed that point mutations affecting FAK catalytic activity ( R 454 ) or Y 925 phosphorylation ( F 925 ) disrupted the ability of FAK to promote MAPK and VEGF associated tumor growth . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
The expression of beta ( 1 ) integrin receptor , as well as Sos 1 and phosphorylated MAPK , ERK ( 1 ) and ERK ( 2 ) but not FAK , Shc , and Grb 2 was significantly decreased in cells incubated for 24h with 20 microM AB 4 compared to the control , not treated cells , whereas in the same conditions melphalan did not evoke any changes in expression of all these signaling proteins , as shown by Western immunoblot analysis . ^^^
Interacting proteins: Q658W2 and P62993 Pubmed SVM Score :0.0
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