Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.50989191
In these experiments , the 130 kDa tyrosine phosphorylated protein was shown to immunoprecipitate with antibody to the cas antigen ( crk associated substrate ) and with antibody to the p 130 tyrosine phosphorylated protein described as undergoing tyrosine phosphorylation in src transformed cells . 0.50989191^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.81273745
Integrin mediated cell adhesion promotes tyrosine phosphorylation of p130Cas , a Src homology 3 containing molecule having multiple Src homology 2 binding motifs . p130Cas ( Cas ) has been recently identified as a 130 kDa protein that is highly phosphorylated on tyrosine residues and is stably associated with p47v crk ( 5 Crk ) and p60v src ( 5 Src ) oncogene products in cells transformed by the respective genes . 0.81273745^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.61606449
Src specifically associates with p 130 Crk associated substrate ( Cas ) in a manner dependent upon Cas phosphorylation , suggesting that Src is responsible for Cas tyrosine phosphorylation . 0.61606449^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.66306192
In an effort to understand the mechanisms of processive phosphorylation , we have explored the regions of Cas necessary for interaction with Src using the yeast two hybrid system . 0.66306192^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.58978399
The association between Src and Cas enhances Src kinase activity , and like Cas , Src plays an important role in cell proliferation and migration . 0.58978399^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.62342376
Physical and functional interactions between Cas and c Src induce tamoxifen resistance of breast cancer cells through pathways involving epidermal growth factor receptor and signal transducer and activator of transcription 5b . 0.62342376^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src kinase plays an essential role in integrin mediated tyrosine phosphorylation of Crk associated substrate p130Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Introduction of p130cas signaling complex formation upon integrin mediated cell adhesion : a role for Src family kinases . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
FAK / Src association activates both kinases , which act on the potential substrates tensin , paxillin and p130cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The activated FAK / Src complex acts on potential substrates tensin , paxillin and p130cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Further , we found by immunoprecipitation experiments that the 120 kDa protein was p130cas , a crk associated src substrate . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Molecular basis for regulation of Src by the docking protein p130Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Of the signaling molecules investigated in this study , Src seemed to associate with Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
By contrast , Cas mediated uptake in the absence of Fak requires Crk as well as the protein tyrosine kinases Pyk 2 and Src . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas interacts with focal adhesion plaques and is phosphorylated by the tyrosine kinases FAK and Src . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
PYK 2 has ligand sequences for Src homology 2 and 3 ( SH 2 and SH 3 ) , and has binding sites for paxillin and p 130 ( cas ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
PAF exposure induced binding of p 130 ( Cas ) , Src , SHC , and paxillin to FAK . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The p 130 ( designated Cas for Crk associated substrate ) is a common cellular target of phosphorylation signal via 5 Crk and 5 Src oncoproteins , and its unique structure indicates the possible role of p130Cas in assembling signals from multiple SH 2 containing molecules . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Complexes of focal adhesion kinase ( FAK ) and Crk associated substrate ( p 130 ( Cas ) ) are elevated in cytoskeleton associated fractions following adhesion and Src transformation . ^^^ The focal adhesion kinase ( FAK ) and Crk associated substrate , p 130 ( Cas ) ( Cas ) , have been implicated in diverse signaling pathways including those mediated by integrins , G protein coupled receptors , tyrosine kinase receptors , and the 5 src and 5 crk oncogenes . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Ligation of the T cell antigen receptor induces tyrosine phosphorylation of p105CasL , a member of the p130Cas related docking protein family , and its subsequent binding to the Src homology 2 domain of c Crk . p105CasL ( CasL ) is a recently identified signaling molecule closely related to the p130Cas ( Crk associated substrate ) docking protein . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Invest . 98 , 2623 2631 ) . p 130 Crk associated substrate ( Cas ) , a putative c Src substrate , was originally identified as a highly phosphorylated protein that is localized to focal adhesions and acts as an adapter protein . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Several lines of evidence indicate that the adapter molecule p130CAS ( crk associated substrate ( CAS ) ) is required for src mediated cellular transformation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Crk associated substrate ( Cas ) lymphocyte type ( Cas L ) is a 105 kDa cytoplasmic protein consisting of Src homology 3 domain and multiple YXXP motifs ( substrate domain ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Crk associated substrate ( p 130 ( Cas ) , Cas ) is a docking protein first recognized as having elevated phosphotyrosine content in mammalian cells transformed by 5 Src and 5 Crk oncoproteins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Abbreviations : CAS , CRK associated substrate ; CH , calponin homology domain ; CSK , C terminal SRC kinase ; E 6 , Papillomavirus E 6 protein ; FAK , focal adhesion kinase ; GIT , GRK interacter ; GPCR , heterotrimeric G protein coupled receptor ; GRK , G protein coupled receptor kinase ; MAPK , mitogen activated protein kinase ( ERK , p 38 , JNK ) ; PAK , p 21 activated kinase ; PBS , paxillin binding subdomain ; PIX , PAK interacting exchange factor ; PKL , paxillin kinase linker ; POR 1 , partner of Rac ; PS , phosphoserine ; PT , phosphothreonine ; PY , phosphotyrosine ; RTK , growth factor receptor tyrosine kinase ; SH , SRC homology domain . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In this study , we report that the Src substrate Cas ( p 130 Crk associated substrate ) associates with protein phosphatase 2A ( PP2A ) , a serine / threonine phosphatase . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Our results portray FAK as a major 5 Src substrate that also plays a role in recruiting 5 Src to phosphorylate substrates CAS ( Crk associated substrate ) and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The Crk associated substrate ( Cas ) is a unique docking protein that possesses a repetitive stretch of tyrosine containing motifs and an Src homology 3 ( SH 3 ) domain . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Previously , we showed that flow mediated tyrosine phosphorylation of p 130 Crk associated substrate ( Cas ) required calcium dependent c Src activation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src family kinases recruited to the Tyr 397 site phosphorylate two FAK interacting proteins , Crk associated substrate ( CAS ) and paxillin , which results ultimately in regulation of Rho family GTPases contributing to cell motility . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src activation failed to increase the high basal tyrosine phosphorylation of the Crk associated substrate , CAS , found in FAK / MEF , indicating that CAS phosphorylation alone is insufficient to induce motility in the absence of FAK or 5 Src induced cytoskeletal remodeling . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Blockade of 5 Src stimulated tumor formation by the Src homology 3 domain of Crk associated substrate ( Cas ) . ^^^ Crk associated substrate ( Cas ) is highly phosphorylated by 5 Src and plays a critical role in 5 Src induced cell transformation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Crk associated substrate ( p 130 ( CAS ) or CAS ) is a major integrin associated Src substrate that undergoes tyrosine phosphorylation at multiple YXXP motifs in its substrate domain ( SD ) to create docking sites for SH 2 containing signaling effectors . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
CAS ( ' Crk associated substrate ' ) is an Src substrate found at sites of integrin mediated cell adhesion and linked to cell motility and survival . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Crk associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC transformed cells . ^^^ Crk associated substrate ( CAS , p130Cas ) is a major tyrosine phosphorylated protein in cells transformed by 5 crk and 5 src oncogenes . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
RESULTS : CN binding to integrins can mimic the intracellular signaling cascade evoked by FN , because the phosphorylation of the key signaling proteins focal adhesion kinase , paxillin , and p 130 Crk associated substrate and the association of Src with focal adhesion kinase are similar . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Complex formation of FAK with JSAP 1 and p 130 Crk associated substrate ( p 130 ( Cas ) ) resulted in augmentation of FAK activity and phosphorylation of both JSAP 1 and p 130 ( Cas ) , which required p 130 ( Cas ) hyperphosphorylation and was abolished by inhibition of Src . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The Src tyrosine kinase phosphorylates specific sites on the focal adhesion adaptor protein Crk associated substrate ( Cas ) to promote nonanchored cell growth and migration . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The screen identified two proteins that interact with FAK via their Src homology 3 ( SH 3 ) domains : a 5 Crk associated tyrosine kinase substrate ( Cas ) , p130Cas , and a still uncharacterized protein , FIPSH 3 2 , which contains an SH 3 domain closely related to that of p130Cas . ^^^ The stable interaction between p130Cas and FAK emerges as a likely key element in integrin mediated signal transduction and further represents a direct molecular link between the 5 Src and 5 Crk oncoproteins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We show in this report that two 5 src substrate proteins , p130Cas and cortactin , become tyrosine phosphorylated during integrin mediated cell adhesion to extracellular matrix substrata and upon cell attachment onto immobilized anti integrin antibodies . ^^^ Tyrosine phosphorylation of p130Cas and cortactin coincides with tyrosine phosphorylation of focal adhesion kinase during integrin mediated cell adhesion but is independent of cell adhesion in 5 src transformed cells . ^^^ The tyrosine phosphorylated sites in p130Cas and cortactin may serve as binding sites for proteins containing Src homology 2 domains , as is the case with two other integrin regulated docking proteins , focal adhesion kinase and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Direct binding of C terminal region of p130Cas to SH 2 and SH 3 domains of Src kinase . p130Cas is a major tyrosine phosphorylated protein that tightly binds 5 Crk in 5 crk transformed cells and 5 Src in 5 src transformed cells . ^^^ The `` substrate domain ' ' of p130Cas contains 15 possible Src homology ( SH ) 2 binding motifs , most of which conform to the binding motif for the Crk SH 2 domain . ^^^ Using GST fusion proteins , we revealed that both SH 2 and SH 3 domains of Src bind p130Cas , whereas 5 Crk binds p130Cas through its SH 2 domain . ^^^ We located the binding site of p130Cas for the Src SH 3 domain at the sequence RPLPSPP in the region near its C terminus . ^^^ Mutations within this sequence or at Tyr 762 of p130Cas caused a significant reduction in the association of p130Cas with Src , and no association was detected when both of them were deleted . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Coordinate activation of c Src by SH 3 and SH 2 binding sites on a novel p130Cas related protein , Sin . ^^^ We found a novel protein , Sin ( Src interacting or signal integrating protein ) , that binds to Src SH 3 with high affinity , contains numerous tyrosine residues in configurations suggestive of SH 2 binding sites , and is related to the 5 Src substrate p130Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Fibronectin stimulated signaling from a focal adhesion kinase c Src complex : involvement of the Grb 2 , p130cas , and Nck adaptor proteins . ^^^ 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 . ^^^ 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 . ^^^ Src 1 298 bound to both FAK and p130cas and promoted FAK association with p130cas in vivo . ^^^ FAK was observed to phosphorylate p130cas in vitro and could thus phosphorylate p130cas upon FN stimulation of the Src 1 298 expressing cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The cellular transformation by 5 Src or 5 Crk induces tyrosine phosphorylation of a common substrate molecule , p130Cas ( Cas ) , which tightly binds these oncoproteins in vivo . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Although 5 src is a more potent inducer of tyrosine phosphorylation than c src 527 , the extent of phosphorylation of either insulin receptor substrate 1 or Shc , two of the major substrates of the IGF 1 receptor , does not seem sufficiently different to explain the qualitative difference in soft agar growth . 5 src , however , is considerably more efficient than c src 527 in its ability to tyrosyl phosphorylate , in R cells , the focal adhesion kinase , Stat 1 , and p130cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
However , the N terminal domains of 5 Src can promote tyrosine phosphorylation of certain proteins , in particular p130Cas , even when expressed in the absence of the catalytic domain , indicating that the N terminal domains of 5 Src have effects that are independent of the catalytic domain . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In the 10T model , preferred substrates of c Src are almost exclusively comprised of those molecules that associate with the actin cytoskeleton or with focal adhesions , such as cortactin , p190RhoGAP , and p130CAS , while preferred substrates of the EGF receptor include the receptor itself , SHC , phospholipase C gamma and p62DOK . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Expression of WT PTP1B reduces formation of p130Cas Crk complexes and inhibits mitogen activated protein kinase activation by Src and Crk . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The phosphorylation was blocked by the specific PKC inhibitor GF 109203X , and transient transfection with active PKC epsilon induced p130cas tyrosine phosphorylation . pp60c src , known to directly phosphorylate p130cas in other cell systems , was not activated after stimulation with TPA or bFGF / IGF 1 for up to 30 min , and the initial p130cas phosphorylation was resistant to the Src family kinase inhibitor herbimycin A . ^^^ Also , overexpression of src induced phosphorylation of p130cas . p130cas protein and phosphorylated p130cas were present in growth cones isolated from differentiated SH SY5Y cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cardiovascular anomaly , impaired actin bundling and resistance to Src induced transformation in mice lacking p130Cas . p130Cas ( Cas ) , the protein encoded by the Crkas gene ( also known as Cas ) , is an adaptor molecule with a unique structure that contains a Src homology ( SH ) 3 domain followed by multiple YXXP motifs and a proline rich region . ^^^
Interacting proteins: P56945 and P12931 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: P56945 and P12931 Pubmed SVM Score :0.0
These results suggest that PKC activation ( but not Ca2+ mobilization ) is involved in PYK 2 tyrosine phosphorylation and that PYK 2 associates with Src without PYK 2 tyrosine phosphorylation or p130Cas involvement in platelets . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In this report , we provide evidence that the protein tyrosine kinase Src and adaptor proteins Grb 2 , Crk , and p130Cas act as downstream mediators of Pyk 2 leading to the activation of extracellular signal regulated kinase ( ERK ) and c Jun amino terminal kinase ( JNK ) . ^^^ Pyk 2 induced activation of Src is necessary for phosphorylation of Shc and p130Cas and their association with Grb 2 and Crk , respectively , and for the activation of ERK and JNK cascades . ^^^ Grb 2 with a deleted carboxyl terminal Src homology 3 domain partially blocked Pyk 2 induced ERK and JNK pathways , whereas expression of dominant interfering mutants of p130Cas or Crk specifically inhibited JNK but not ERK activation by Pyk 2 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Focal adhesion kinase ( FAK ) plays a prominent role in the adhesion signaling pathway through its tyrosine kinase activity and protein protein interaction with other signaling molecules , including src , paxillin , and p130CAS , and other proteins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Immunocytochemistry , sucrose density gradient sedimentation , co immunoprecipitation analyses and in vitro binding assays have shown that polycystin 1 associates with the focal adhesion proteins talin , vinculin , p130Cas , FAK , alpha actinin , paxillin and pp60c src in subconfluent normal human fetal collecting tubule ( HFCT ) epithelia when cell matrix interactions predominate . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Gastrin and CCK also induce rapid Rho dependent actin remodeling and coordinate tyrosine phosphorylation of cellular proteins including the non receptor tyrosine kinases p125fak and Src and the adaptor proteins p130cas and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Interestingly , tyrosine phosphorylation of paxillin , but not p130cas , was induced by expression of Src FAT , suggesting a potential role of paxillin in mediating stimulation of cell migration by the chimeric molecule . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Integrin induced epidermal growth factor ( EGF ) receptor activation requires c Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines . ^^^ We show that in the early phases of cell adhesion integrins associate with EGF receptors on the cell membrane in a macromolecular complex including the adaptor protein p130Cas and the c Src kinase , the latter being required for adhesion dependent assembly of the macromolecular complex . ^^^ We also show that the integrin cytoplasmic tail , c Src kinase , and the p130Cas adaptor protein are required for phosphorylation of EGF receptor in response to integrin mediated adhesion . ^^^ Therefore these data indicate that integrin mediated adhesion induces assembly of a macromolecular complex containing c Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosine residues . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Paxillin associates with numerous signaling molecules including adaptor molecules ( p130Cas , CRK ) , kinases ( FAK , Pyk 2 , PAK and SRC ) , tyrosine phosphatases ( PTP PEST ) , ARF GAP proteins ( p95pkl , PAG 3 ) and papillomavirus E 6 oncoproteins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In addition , Ang 2 activates many intracellular tyrosine kinases that play a role in growth signaling and inflammation , such as Src , Pyk 2 , p130Cas , FAK and JAK / STAT . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
FRNK expression disrupted the formation of a 5 Src FAK signaling complex , inhibited p130Cas tyrosine phosphorylation , and attenuated 5 Src stimulated ERK and JNK kinase activation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Selective involvement of p130Cas / Crk / Pyk2 / c Src in endothelin 1 induced JNK activation . ^^^ In this report , we investigated the activation and regulation of p130Cas , Crk , Pyk 2 , and c Src by a well known hypertrophic agonist , endothelin 1 ( ET ) , and determined their contributions to the activation of c Jun NH 2 terminal kinase ( JNK ) and extracellular signal regulated kinase ( ERK ) in cardiomyocytes . ^^^ We also observed ET induced temporal associations of Pyk 2 with active c Src , followed by p130Cas with Pyk 2 , c Src , and Crk . ^^^ Collectively , the focal adhesion dependent p130Cas / Crk / Pyk2 / c Src mediated pathway is selectively involved in ET induced JNK activation in cardiomyocytes . . ^^^ This activation of p130Cas was also abrogated by the tetrapeptide RGDS , which disrupts integrin heterodimerization ; cytochalasin D , which depolymerizes the actin cytoskeleton ; or a selective Src family kinase inhibitor , PP 2 , but not by an EGFR inhibitor , AG 1478 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
RGD dose response experiments revealed that c Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase ( FAK ) Tyr 925 phosphorylation . ^^^ Together these data indicate that RGD treatment in cardiomyocytes causes beta 3 integrin activation and c Src sarcolemmal localization , that subsequent c Src activation is accompanied by p130Cas binding and FAK Tyr 925 phosphorylation , and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Possible involvement of calcineurin , protein kinase C , and Src family kinases in angiotensin 2 induced tyrosine phosphorylation of p130cas in rat cardiac muscle . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Both p130Cas and c Cbl have been reported to play critical roles in osteoclast function as downstream targets of c Src kinase . ^^^ These results suggest that in osteoclasts 1 ) tyrosine phosphorylation of p130Cas depends on alpha 5 beta 3 integrin mediated cell adhesion , even in the presence of M CSF ; 2 ) on the other hand , c Cbl phosphorylation is predominantly activated by M CSF and is independent of cell adhesion ; 3 ) lastly , although c Src is essential for both adhesion and M CSF mediated phosphorylation of p130Cas , it is clearly not required for c Cbl phosphorylation in M CSF treated pOCs . ^^^ The purpose of this study was to examine adhesion and macrophage colony stimulating factor ( M CSF ) induced tyrosine phosphorylation of these two molecules in prefusion osteoclasts ( pOCs ) derived from either Src+ / . or Src / mice and to directly compare the roles of p130Cas and c Cbl in osteoclast function . ^^^ In Src deficient pOCs plated on vitronectin , although M CSF highly induces Cbl phosphorylation , it does not affect p130Cas phosphorylation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Vascular endothelial growth factor receptor 2 inhibition also reversed VEGF stimulated phosphorylation of CrkII and its Src homology 2 ( SH 2 ) binding protein p130Cas , which are known to play a pivotal role in regulating endothelial cell migration . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Using these assays , we show that kinases and adaptor molecules , including focal adhesion kinase ( FAK ) , Src , p130CAS , paxillin , extracellular signal regulated kinase ( ERK ) and myosin light chain kinase ( MLCK ) are critical for adhesion turnover at the cell front , a process central to migration . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
A number of signalling molecules were found to be involved in the alpha ( 5 ) beta 3 integrin dependent signalling pathway , including c Src , Pyk 2 and p130Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
A major substrate of c Src kinase activity is the cytoskeletal protein p130Cas , originally identified in 5 Src transformed cells . ^^^ We show that in the human breast carcinoma T47D cells , upon estrogen treatment , p130Cas rapidly and transiently associates with the estrogen receptor alpha in a multi molecular complex containing the c Src kinase and the p 85 subunit of PI 3 kinase . ^^^ Association of p130Cas with the estrogen receptor alpha occurs within 3 minutes of estrogen treatment and is dependent on c Src kinase activation . ^^^ Transient overexpression of p130Cas in T47D cells increases estrogen dependent Src kinase and Erk1 / 2 MAPKs activities and accelerates their kinetics of stimulation . ^^^ Therefore , our data show that the adaptor protein p130Cas associates with the estrogen receptor transducing complex , regulating estrogen dependent activation of c Src kinase and downstream signaling pathways . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src activity is known to be required for the migration of a number of cell types . p130Cas was reported to be essential for cell migration and actin filament reorganization . ^^^ However , precise intracellular mechanisms involving c Src , p130Cas , and MAP kinases in Ang 2 stimulated migration of VSMC have not been well elucidated . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The frontier includes characterization of how scaffolding / adapter proteins , such as cbl , gab , grb , p130Cas , and shc , as well as itam containing proteins and nonreceptor tyrosine kinase adapters of the src and syk families , delimit and integrate signals of multiple receptors to bring about specific outcomes . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The Crk associated tyrosine kinase substrate p130cas ( CAS ) is a docking protein containing an SH 3 domain near its N terminus , followed by a short proline rich segment , a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP , a serine rich region and a carboxy terminal domain , which possesses consensus binding sites for the SH 2 and SH 3 domains of Src ( YDYV and RPLPSPP , respectively ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We have previously observed that collagen 4 regulates Caco 2 intestinal epithelial cell spreading and migration via Src kinase and stimulates Src dependent tyrosine phosphorylation of p130cas . ^^^ Although p130cas siRNA inhibited cell spreading on collagen 4 by 33 % , three different paxillin siRNAs did not inhibit cell spreading . p130cas siRNA did not affect Src Tyr 416 or Src Tyr 527 phosphorylation , FAK Tyr 397 phosphorylation , or Src dependent phosphorylation of FAK Tyr 925 , suggesting that p130cas did not inhibit cell spreading by altering FAK or Src activity . ^^^ In contrast , expression of rat p130cas from which the Src phosphorylated substrate domain was deleted did not rescue siRNA inhibition of cell spreading . ^^^ These results suggest that Src may regulate Caco 2 migration on collagen 4 via both p130cas and paxillin but that Src phosphorylation of p130cas is more important for this process . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Inhibition of Kit modulated phosphorylation dependent interactions with pathways controlling focal adhesion ( paxillin , leupaxin , p130CAS , FAK 1 , the Src family kinase Lyn , Wasp , Fhl 3 , G25K , Ack 1 , Nap 1 , SH3P12 / ponsin ) and septin actin complexes ( NEDD 5 , cdc 11 , actin ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In the present study , we investigated the effect of neonatal cerebral hypoxia ischemia ( HI ) on levels and tyrosine phosphorylation of focal adhesion kinase and the interaction of this enzyme with Src protein tyrosine kinase and adapter protein p130Cas , involved in FAK mediated signaling pathway . ^^^ Concomitantly a decreased association of FAK with its investigated molecular partners , Src kinase and p130Cas protein has been observed . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Phosphorylation of p130Cas by NPM ALK was partially independent from Src ( tyrosine kinase pp60c src ) kinase activity , as it was still detectable in Syf / cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Ang 2 induced AT1R activation via Gq / 11 stimulates phospholipases A 2 , C , and D , and activates inositol trisphosphate / Ca2+ signaling , protein kinase C isoforms , and MAPKs , as well as several tyrosine kinases ( Pyk 2 , Src , Tyk 2 , FAK ) , scaffold proteins ( G protein coupled receptor kinase interacting protein 1 , p130Cas , paxillin , vinculin ) , receptor tyrosine kinases , and the nuclear factor kappaB pathway . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Notably , alpha 4 stimulated cell motility was inhibited by catalytically inactive receptor protein tyrosine phosphatase alpha overexpression and blocked by the p50Csk phosphorylation of c Src at Tyr 529 . alpha4beta1 stimulated cell motility of triple null Src ( / ) , c Yes ( / ) , and Fyn ( / ) fibroblasts was dependent on c Src reexpression that resulted in p130Cas tyrosine phosphorylation and Rac GTPase loading . ^^^ As p130Cas phosphorylation and Rac activation are common downstream targets for alpha5beta1 stimulated FAK activation , our results support the existence of a novel alpha 4 cytoplasmic domain connection leading to c Src activation which functions as a FAK independent linkage to a common motility promoting signaling pathway . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Since the binding of p130cas and Src to PTP1B is dependent upon these proline residues , we assayed the regulation of PTP1B in mouse embryo fibroblasts deficient in these proteins . ^^^ We found that neither p130cas nor Src is required for the inhibition of PTP1B activity by adhesion to extracellular matrix proteins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
CD 82 expression also reduced integrin induced activation and phosphorylation of the cytoplasmic tyrosine kinase Src , and its downstream substrates p130Cas and FAK Y 861 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The stretch activated substrate of Fyn and c Src , p130Cas , is also required for a rigidity response and it is phosphorylated at the leading edge in a Fyn dependent process . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Association with expression of abl , ras , fes , src , erbB , and Cas NS 1 oncogenes but not with myc . ^^^ This antigen was expressed on many pre B and B cell lymphomas , but not on A MuLV transformed fibroblasts , T cell lymphomas , or myelomonocytic leukemias , gp 160 ( 6C3 ) was expressed by most early B lineage spontaneous tumors , and early B tumors induced by replication defective MuLV containing oncogenes the products of which are associated with the cytoplasmic aspect of the plasma membrane , i . e . , fes , abl , H ras , bas , src , erbB , and Cas NS 1 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The novel catenin p120cas binds classical cadherins and induces an unusual morphological phenotype in NIH3T3 fibroblasts . p120cas ( CAS ) is a tyrosine kinase substrate whose phosphorylation has been implicated in cell transformation by Src and in ligand induced signaling through the EGF , PDGF , and CSF 1 receptors . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Direct binding of the proline rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p 130 ( Cas ) . ^^^ These results suggest that the proline rich domain between amino acids 301 and 315 in PTP1B binds Src homology 3 containing proteins and that p 130 ( Cas ) may be a physiological target of this phosphatase in cells . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
A signaling partnership is formed between FAK and Src family kinases , leading to tyrosine phosphorylation of FAK and associated ' docking ' proteins Cas and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Additionally , two proteins that indicate activation of src , p 85 cortactin and p 120 ( cas ) , are phosphorylated in at least six of the tumor derived cell lines , although to a lesser extent in line E2T . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas was originally identified as a major tyrosine phosphorylated protein in 5 Crk and 5 Src transformed cells . ^^^ However , in 527F c Src transformed cells , Cas was localized mainly to podosomes , where the focal adhesion proteins are assembled . ^^^ The localization of Cas to focal adhesions was also observed in cells expressing the kinase negative 527F / 295M c Src . ^^^ A series of analyses with deletion mutants expressed in various cells revealed that the SH 3 domain of Cas is necessary for its localization to focal adhesions in nontransformed cells while both the SH 3 domain and the C terminal Src binding domain of Cas are required in 527F c Src transformed cells and fibronectin stimulated cells . ^^^ In addition , the localization of Cas to focal adhesions was abolished in Src negative cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Furthermore , Tyr 402 , which mediates the binding of RAFTK to c Src kinase , was required for the phosphorylation of the C terminal domain of p 130 ( Cas ) . ^^^ These data suggest that RAFTK itself is sufficient for HEF 1 phosphorylation , whereas a cooperation between RAFTK and Src kinases is required for the complete phosphorylation of p 130 ( Cas ) . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Furthermore , the phosphorylated YDYVHL sequence is a binding site for Src family protein tyrosine kinases , and the recruited Src family kinase phosphorylates the other tyrosine residues within Cas . ^^^ These findings strongly suggest that FAK initiates integrin mediated tyrosine phosphorylation of Cas proteins ; then , Src family tyrosine kinases , which are recruited to phosphorylated Cas and FAK , further phosphorylate Cas proteins . . ^^^
Interacting proteins: P56945 and P12931 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 ) . ^^^ This mutation did not affect FAK kinase activity , autophosphorylation , or Src association but did significantly reduce p 130 ( Cas ) association with FAK . ^^^ Furthermore , FAK expression in CHO cells increased tyrosine phosphorylation of p 130 ( Cas ) and its subsequent binding to several SH 2 domains , which depended on both the p 130 ( Cas ) binding site and the Src binding site . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas L contains possible multiple binding sites for the Src homology ( SH ) 2 domains of various signaling molecules , and appears to be involved in signal transduction through phosphorylated tyrosine mediated protein protein interaction . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In the present study , we found that the 120 k protein was a Crk associated Src substrate , p 130 ( cas ) . ^^^ Using the substrate region of p 130 ( cas ) as the substrate , we found that Fyn and Src were activated on stimulation with KCl . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In OCLs derived from Src ( / ) mice , in which osteoclast activity is severely compromised , tyrosine phosphorylation of Cas was markedly reduced . ^^^ These findings suggest that Src dependent tyrosine phosphorylation of Cas is involved in the adhesion induced actin organization associated with osteoclast activation . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
By analyzing FAK deficient ( FAK / ) cells transiently expressing Cas mutant proteins , we demonstrate here that the Src homology 3 ( SH 3 ) domain of Cas is indispensable for adhesion mediated Cas phosphorylation in this mutant cell line . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The insulin induced decrease in the CrkII p 130 ( cas ) association was further confirmed by Far Western Blot analysis with the Src homology 2 ( SH 2 ) domain of CrkII . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In HIRY / F2 cells expressing a mutant insulin receptor lacking a binding site of SHP 2 , a protein tyrosine phosphatase containing src homology 2 ( SH 2 ) regions , insulin accelerated phosphorylation of Cas , as did IGF 1 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Both the c Src and c Fyn tyrosine kinases are tyrosine phosphorylated and activated by cellular hGH stimulation and form part of the multiprotein signaling complex as does tensin , paxillin , IRS 1 , the p 85 subunit of phosphatidylinositol 3 kinase , C3G , SHC , Grb 2 , and Sos 1 . c Cbl and Nck are also tyrosine phosphorylated by cellular stimulation with hGH and associate with the p 130 ( Cas ) CrkII complex . c Jun N terminal kinase / stress activated protein kinase ( JNK / SAPK ) is activated in response to hGH in accordance with the formation of the abovementioned signaling complex , and hGH stimulated JNK / SAPK activity is increased in CrkII overexpressing NIH3T3 cells compared with vector transfected NIH3T3 cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The expression of other Src substrates and interacting proteins , such as p 120 Cas , p 130 Cas , vinculin , Fak kinase , and the p 85 phosphatidylinositol 3 kinase subunit either did not change or slightly increased during PMA treatment . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
A dominant negative form of Cas in turn blocked the integrin , but not epidermal growth factor nor 5 Src mediated JNK activation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Dissociation of FAK / p130 ( CAS ) / c Src complex during mitosis : role of mitosis specific serine phosphorylation of FAK . ^^^ First , the association of FAK with CAS or c Src is greatly inhibited , with levels decreasing to 16 and 13 % of the interphase levels , respectively . ^^^ Mitosis specific phosphorylation is responsible for the disruption of FAK / CAS binding because dephosphorylation of mitotic FAK in vitro by protein serine / threonine phosphatase 1 restores the ability of FAK to associate with CAS , though not with c Src . ^^^ These results suggest that mitosis specific modification of FAK uncouples signal transduction pathways involving integrin , CAS , and c Src , and may maintain FAK in an inactive state until post mitotic spreading . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Tight junction permeability may be independently controlled , but is dependent on the adherens junction , where adhesion is achieved through homotypic interaction of cadherins , which in turn are associated with cytoplasmic proteins , the catenins . p 120 , also termed p 120 ( cas ) / p120 ( ctn ) , and its splice variant , p 100 , are catenins . p 120 , originally discovered as a substrate of the tyrosine kinase Src , is also a target for a protein kinase C stimulated pathway in epithelial cells , causing its serine / threonine dephosphorylation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In the PTP PEST ( / ) cells , an increase in affinity for the SH 2 domains of Src and Crk towards p 130 ( CAS ) was also observed . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
These results strongly suggest that cyclic stretch induces the activation of pp 60 ( src ) and that pp 60 ( src ) is indispensable for the tyrosine phosphorylation of pp 130 ( CAS ) , pp 125 ( FAK ) and paxillin followed by the orienting response in 3Y1 fibroblasts . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Together , these results strongly suggest that PI3K binding is required for FAK to promote cell migration and that the binding of Src and p 130 ( Cas ) to FAK may not be sufficient for this event . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In response to adhesion on a fibronectin substrate , RPTPalpha / fibroblasts also exhibited characteristic deficiencies in integrin mediated signalling responses , such as decreased tyrosine phosphorylation of the c Src substrates Fak and p 130 ( cas ) , and reduced activation of extracellular signal regulated ( Erk ) MAP kinases . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas ligand with multiple Src homology ( SH ) 3 domains ( CMS ) is an ubiquitously expressed signal transduction molecule that interacts with the focal adhesion protein p 130 ( Cas ) . ^^^ The latter sequences mediate the binding to the SH 3 domains of p 130 ( Cas ) , Src family kinases , p 85 subunit of phosphatidylinositol 3 kinase , and Grb 2 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Integrin mediated stimulation of JNK required the association of focal adhesion kinase ( FAK ) with a Src kinase and p 130 ( CAS ) , the phosphorylation of p 130 ( CAS ) , and subsequently , the recruitment of Crk . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The focal adhesion protein p 130 ( Cas ) was identified as a substrate for the protein tyrosine phosphatase ( PTP ) PEST , and the specificity of this interaction is mediated by a dual mechanism involving a Src homology 3 domain mediated binding and PTP domain recognition . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In addition , we found that phosphorylation of FAK or p 130 ( cas ) was not affected by the expression of either Grb 7 or its SH 2 domain alone , suggesting that Grb 7 is downstream of FAK and does not compete with Src for binding to FAK in vivo . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In this study , we have demonstrated that UV irradiation induced cleavage of FAK and two of its interacting proteins Src and p 130 ( Cas ) in Madin Darby canine kidney cells , concomitant with an increase in cell death . ^^^ Moreover , the expression of the Src homology 3 domain of p 130 ( Cas ) , which competed with endogenous p 130 ( Cas ) for FAK binding , abrogated the FAK promoted cell survival . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas mediates transcriptional activation of the serum response element by Src . ^^^ The Src substrate p 130 ( Cas ) is a docking protein containing an SH 3 domain , a substrate domain that contains multiple consensus SH 2 binding sites , and a Src binding region . ^^^ We have examined the possibility that Cas plays a role in the transcriptional activation of immediate early genes ( IEGs ) by 5 Src . ^^^ An SRE transcriptional reporter was used to study the ability of Cas to mediate Src induced SRE activation . ^^^ Coexpression of 5 Src and Cas led to a threefold increase in SRE dependent transcription over the level induced by 5 Src alone . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We demonstrate the utility of these probes in a dual binding assay ( suitable for high throughput screening ) to study the interactions of various peptides with these domains , including a sequence from the rat protein p 130 ( CAS ) which has been reported to bind simultaneously to both Src SH 3 and SH 2 domains . ^^^ Utilizing this dual binding assay , we confirm that sequences from p 130 ( CAS ) can simultaneously bind Src via both its SH 3 and its SH 2 domains . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src and Cas mediate JNK activation but not ERK1 / 2 and p 38 kinases by reactive oxygen species . c Jun NH ( 2 ) terminal kinase ( JNK ) is activated by a number of cellular stimuli such as inflammatory cytokines and environmental stresses . ^^^ Because recent reports showed that expression of Cas , a putative Src substrate , stimulates JNK activation , we hypothesized that the Src kinase family and Cas would be involved in JNK activation by reactive oxygen species . ^^^ An essential role for both Src and Cas was demonstrated . ^^^ Finally , the importance of Src was further supported by the inhibition of both H ( 2 ) O ( 2 ) mediated Cas tyrosine phosphorylation and Cas . ^^^ These results demonstrate an essential role for Src and Cas in H ( 2 ) O ( 2 ) mediated activation of JNK and suggest a new redox sensitive pathway for JNK activation mediated by Src . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Furthermore , several signaling and adaptor molecules were found to be involved in alphavbeta 3 integrin dependent signaling pathways , including phosphatidylinositol 3 kinase , c Src , PYK 2 and p 130 ( cas ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
These include bombesin induced assembly of focal adhesions , formation of parallel arrays of actin stress fibers , increase in the tyrosine phosphorylation of focal adhesion kinase ( FAK ) , p 130 ( Cas ) , and paxillin , and formation of a complex between FAK and Src . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We found that at concentrations as low as 1 nM , soluble contortrostatin activates integrin signals leading to increased tyrosine phosphorylation of FAK and CAS , and that these signals are abolished by inhibiting Src family kinases . ^^^ We propose that the homodimeric nature of contortrostatin imparts the ability to crosslink alphavbeta 3 integrins , causing Src activation and hyperphosphorylation of FAK and CAS . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Regulation of c SRC activity and function by the adapter protein CAS . ^^^ The activities of these kinases are regulated by intramolecular interactions and by heterologous binding partners that modulate the transition between active and inactive structural conformations . p 130 ( CAS ) ( CAS ) binds directly to both the SH 2 and SH 3 domains of c SRC and therefore has the potential to structurally alter and activate this kinase . ^^^ In this report , we demonstrate that overexpression of full length CAS in COS 1 cells induces c SRC dependent tyrosine phosphorylation of multiple endogenous cellular proteins . ^^^ A carboxy terminal fragment of CAS ( CAS CT ) , which contains the c SRC binding site , was sufficient to induce c SRC dependent protein tyrosine kinase activity , as measured by tyrosine phosphorylation of cortactin , paxillin , and , to a lesser extent , focal adhesion kinase . ^^^ A single amino acid substitution located in the binding site for the SRC SH 3 domain of CAS CT disrupted CAS CT ' s interaction with c SRC and inhibited its ability to induce tyrosine phosphorylation of cortactin and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase ( FAK ) at Tyr 397 and Tyr 925 , c Src at Tyr 416 , recruitment of the adapter proteins p 130 ( Cas ) , Shc , and Nck , and activation of the extracellular regulated kinases ERK1 / 2 . ^^^ In RGD stimulated collagen embedded cells , FAK was phosphorylated only at Tyr 397 and c Src association occurred without Tyr 416 phosphorylation and p 130 ( Cas ) association . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Phosphorylation of the c Src cellular substrates paxillin , p 130 ( cas ) , and Stat 3 was also inhibited at concentrations < 1 microM . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
To this end , we used full length and truncated versions of the multiadapter molecules Cas and Sin to activate c Src , and we examined the intracellular pathways that mediate Src signaling under these conditions . ^^^ Src signaling induced by the adapters Sin and Cas is mediated by Rap 1 GTPase . ^^^ In addition , we show that Sin and Cas induced Src signaling , as assayed by transcriptional activation , is exclusively mediated through a pathway that involves the adapter Crk and the GTP binding protein Rap 1 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We have previously reported that engagement of ( alpha ) ( 5 ) ( beta ) ( 3 ) integrin in osteoclasts induces tyrosine phosphorylation and activation of the adhesion kinase PYK 2 and the adaptor protein p 130 ( Cas ) in a Src dependent manner . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The 130 kDa phosphotyrosine containing protein was identified by immunoprecipitation to be Cas , a crk associated src substrate . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
PKC dependent activation of FAK and src induces tyrosine phosphorylation of Cas and formation of Cas Crk complexes . ^^^ The activity of two protein tyrosine kinases , Src and FAK , was shown to be necessary and sufficient for TPA induced Cas phosphorylation . ^^^ We propose that the PKC dependent phosphorylation of Cas by Src and FAK promotes the establishment of Cas Crk complexes and that these interactions may play an important role in regulating the actin cytoskeleton during neuronal differentiation . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src deficient cells attach to but do not spread on vitronectin ( Vn ) coated surfaces and , contrary to wild type cells , their adhesion does not lead to tyrosine phosphorylation of molecules activated by adhesion , including PYK 2 , p 130 ( Cas ) , paxillin , and PLC gamma . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
This gene encodes an SH 3 domain containing adapter protein with sequence similarity to the CD2AP ( CD 2 adapter protein ) and CMS ( Cas ligand with multiple Src homology ) genes . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The function of nephrocystin is presently unknown , but the presence of a Src homology 3 domain and its recently described interaction with p 130 ( Cas ) suggest that nephrocystin is part of the focal adhesion signaling complex . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas , alone or in cooperation with Src , modulated basal and ET stimulated atrial natriuretic peptide ( ANP ) gene promoter activity , a marker of cardiac hypertrophy . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The src family kinase selective inhibitor PP 1 reduced carbachol stimulated tyrosine phosphorylation of FAK , Cas , and paxillin by 50 to 75 % . ^^^ Thus , muscarinic receptors activate protein tyrosine phosphorylation in differentiated cells , and the tyrosine phosphorylation of FAK , Cas , and paxillin , but not ERK1 / 2 , is mediated by a src family tyrosine kinase activated in response to stimulation of muscarinic receptors . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
PR 39 , which is an endogenous antimicrobial peptide , can bind to Src homology 3 domains of the NADPH complex protein p 47 ( phox ) and the signaling adapter protein p 130 ( Cas ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Here we show that gelsolin coprecipitates some of the focal adhesion associated proteins such as c Src , phosphoinositide 3 kinase ( PI3K ) , p 130 ( Cas ) , focal adhesion kinase , integrin alpha ( 5 ) beta ( 3 ) , vinculin , talin , and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Treatment of A 549 cells with FAK antisense ( ISIS 15421 ) but not a mismatched control ( ISIS 17636 ) oligonucleotide resulted in reduced EGF stimulated p 130 ( Cas ) Src complex formation , c Jun NH ( 2 ) terminal kinase ( JNK ) activation , directed cell motility , and serum stimulated cell invasion through Matrigel . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src . ^^^ Aberrant CAS tyrosine phosphorylation may contribute to cell transformation by certain oncoproteins , including 5 Crk and 5 Src , and to tumor growth and metastasis . ^^^ CAS makes multiple interactions , direct and indirect , with the tyrosine kinases Src and focal adhesion kinase ( FAK ) , and as a result of this complexity , several plausible models have been proposed for the mechanism of CAS SD phosphorylation . ^^^ The objective of this study was to provide experimental tests of these models in order to determine the most likely mechanism ( s ) of CAS SD tyrosine phosphorylation by FAK and Src . ^^^ In vitro kinase assays indicated that FAK has a very poor capacity to phosphorylate CAS SD , relative to Src . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
By purification / mass spectrometry and by immunodepletion , p 130 protein was identified as p 130 Cas ( Crk associated protein ) , a Src substrate and a protein involved in signaling by cell adhesion receptors , integrins . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Activated Src ( SrcY529F ) as well as activation of putative Src signaling mediators ( Fak , Cas , Crk / CrkL , C3G , and Rap 1 ) blocked the effect of FA Csk in a manner dependent on Rap 1 . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In contrast , Src mutations in the SH 2 or SH 3 domain greatly reduced binding to FAK , Cas , and paxillin but had little effect on tyrosine phosphorylation or biological assays . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Herein , we provide cDNA microarray evidence that METH administration caused the induction of c Jun and of other members involved in the pathway leading to c Jun activation [ stress activated protein kinase / Jun N terminal kinase ( JNK 3 ) , Crk associated substrate Cas and c Src ] after environmental stresses or cytokine stimulation . ^^^ Other upstream members of the JNK pathway , including phosphorylated JNKs , mitogen activated protein kinase kinase 4 , mitogen activated protein kinase kinase 7 , Crk 2 , Cas , and c Src were also increased at the protein level . ^^^ Methamphetamine causes coordinate regulation of Src , Cas , Crk , and the Jun N terminal kinase Jun pathway . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Analysis of gene expression profile in p 130 ( Cas ) deficient fibroblasts . p 130 ( Cas ) ( Cas ) is a docking protein that becomes tyrosine phosphorylated in 5 Src or 5 Crk transformed cells and in integrin stimulated cells . ^^^ Cas / fibroblasts show defects in stress fiber formation , cell spreading , cell migration , and transformation by activated Src . ^^^ Activated Src reduced the expression of most of these genes both in Cas / and in Cas + / + fibroblasts . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Involvement of cell cell interactions in the rapid stimulation of Cas tyrosine phosphorylation and Src kinase activity by transforming growth factor beta 1 . ^^^ Here , we report that a rapid and transient tyrosine phosphorylation of Cas is induced by TGF beta 1 and that E cadherin mediated cell cell interaction and the Src kinase pathway are involved in this early TGF beta signaling . ^^^ TGF beta 1 also stimulated Src kinase activity , and specific inhibitors of Src completely blocked the induction of Cas phosphorylation by TGF beta 1 . ^^^ The Cas phosphorylation and Src kinase activation seen in our results were induced in an epithelial phenotype specific manner . ^^^ Stable transfection of E cadherin to L 929 cells and L cells as well as E cadherin blocking assay revealed that E cadherin mediated cell cell interactions were essential for both Cas phosphorylation and Src kinase activation . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We have previously shown that ethanol administration results in tyrosine phosphorylation of the 130 kDa protein in rat brain , and identified the protein as Cas , the crk associated src substrate . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Using various FAK mutants , we found that the simultaneous bindings of Src and p 130 ( cas ) were required for FAK to potentiate cell transformation . ^^^ Expression of FAK related nonkinase , kinase deficient Src , or the Src homology 3 domain of p 130 ( cas ) , which respectively serve as dominant negative versions of FAK , Src , and p 130 ( cas ) , apparently reversed the transformed phenotypes of FAK overexpressed cells upon HGF stimulation . ^^^ Moreover , FAK overexpression was able to enhance HGF elicited signals , leading to sustained activation of ERK , JNK , and AKT , which could be prevented by the expression of the Src homology 3 domain of p 130 ( cas ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Analysis of two known p 130 ( Cas ) associated tyrosine kinases FAK and Src indicated that the regulation of tyrosine phosphorylation of FAK and Src are altered in the tumor cells . ^^^ Inhibition of Src specifically abolished phosphorylation of p 130 ( Cas ) and induced anoikis . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Signaling events downstream of R Ras differed from integrins and K Ras , since pharmacological inhibition of Src or disruption of actin inhibited integrin mediated FAK and p 130 ( Cas ) phosphorylation , focal adhesion formation , and migration in control and K Ras ( 12V ) expressing cells but had minimal effect in cells expressing R Ras ( 38V ) . ^^^ Therefore , signaling from R Ras to FAK and p 130 ( Cas ) has a component that is Src independent and not through classic integrin signaling pathways and a component that is Src dependent . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
The adapter protein Crk Like ( CrkL ) can associate with the Src substrate p 130 ( Cas ) ( Cas ) . ^^^ Consistent with the ability of CrkL to biochemically associate with Cas , we found that Src triggers translocation of CrkL to focal adhesions ( FAs ) in a manner dependent on Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Transient overexpression of FRNK in SMC attenuated autophosphorylation of FAK at Tyr 397 , reduced Src family dependent tyrosine phosphorylation of FAK at Tyr 576 , Tyr 577 , and Tyr 881 , and reduced phosphorylation of the FAK / Src substrates Cas and paxillin . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
However , JNK activation in response to Cr ( 6 ) and exogenous H ( 2 ) O ( 2 ) ( 1 mM ) shared requirements for intracellular thiol oxidation , activation of Src family kinases , and p 130 ( cas ) ( Cas ) . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Src phosphorylates Cas on tyrosine 253 to promote migration of transformed cells . ^^^ Phosphorylation of Cas by Src is an important event leading to cell transformation . ^^^ Using mass spectrometry , we have mapped 11 sites in Cas that are phosphorylated by Src . ^^^ We tested synthetic peptides modeled on Cas phosphorylation sites , and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently . ^^^ Using cells derived from Cas deficient mice , we confirmed that Cas greatly enhanced the ability of Src to transform cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Strong and diffuse c Src expression was identified in 17 of 19 ( 89 % ) node metastases , in 29 of 34 ( 85 % ) Cas , in 26 of 28 ( 93 % ) HGDs , in 18 of 25 ( 72 % ) LGDs , and in 9 of 22 ( 41 % ) IMs . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Further analysis demonstrated that , although TSA reduced the expression of Eps 8 in a dose and time dependent manner , both the protein expression and kinase activity of 5 Src remained constant , and the abundance and phosphotyrosine levels of Src substrates , including cortactin , focal adhesion kinase , p 130 ( Cas ) , paxillin , and Shc , were not altered . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Phosphorylation , by Src family kinases , of multiple tyrosine residues in the CAS substrate domain ( SD ) is a major integrin signaling event that promotes cell motility . ^^^ An analysis of CAS and focal adhesion kinase ( FAK ) variants expressed in CAS and FAK deficient cell lines , respectively , indicated that CAS SD tyrosine phosphorylation is substantially achieved by Src family kinases brought into association with CAS through two distinct mechanisms : direct binding to the CAS Src binding domain and indirect association through a FAK bridge . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Association with Cas also seems to be necessary for EGF induced SHEP 1 tyrosine phosphorylation , which is mediated by a Src family kinase . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We will identify the key players in the integrin mediated signaling pathways involved in cell motility and apoptosis , such as FAK , paxillin and p 130 ( CAS ) , and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In some contexts , steroid receptors interact directly with c Src and other cytoplasmic signaling molecules , such as Shc , PI3K , and p 130 Cas . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In transient transfection experiments with HEK 293 cells , TK 3 phosphorylated the well known Src kinase substrate p 130 Cas , an intracellular scaffolding protein . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
We show that down regulation of PTP1B activity with small molecule inhibitors suppresses cell spreading and migration to fibronectin , increases Tyr ( 527 ) phosphorylation in Src , and decreases phosphorylation of FAK , p 130 ( Cas ) , and ERK1 / 2 . ^^^ We also show that PTP1B forms a complex with Src and p 130 ( Cas ) , and that the proline rich motif PPRPPK ( residues 309 314 ) in PTP1B is essential for the complex formation . ^^^ We suggest that the specificity of PTP1B for Src pTyr ( 527 ) is mediated by protein protein interactions involving the docking protein p 130 ( Cas ) with both Src and PTP1B in addition to the interactions between the PTP1B active site and the pTyr ( 527 ) motif . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas , known to be phosphorylated by c Src , was identified as a major tyrosine phosphorylated protein in differentiating RAW 264 cells and the phosphorylation appeared to be decreased in ADAP knockdown cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
In addition , under anoikis stress , the induction of the Y397F mutant in 5 Src transformed FAK ( / ) cells selectively led to a decrease in the level of p 130 ( Cas ) , but not other focal adhesion proteins such as talin , vinculin , and paxillin . ^^^ These results suggest that FAK may increase the susceptibility of 5 Src transformed cells to anoikis by modulating the level of p 130 ( Cas ) . . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas and c Cbl , known to function in podosomes of osteoclasts , were identified as novel proteins binding to the SHIP SH 2 domain by mass spectrometric analysis , and this interaction appeared to be dependent on the Src kinase activity . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cas coimmunoprecipitates with Src family protein tyrosine kinases , Crk , and cell adhesion molecules and colocalizes with these proteins in granule cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Individual Cas phosphorylation sites are dispensable for processive phosphorylation by Src and anchorage independent cell growth . ^^^ Cas possesses a large central substrate domain containing 15 repeats of the sequence YXXP , which are phosphorylated by Src . ^^^ We showed previously that Src catalyzes the multisite phosphorylation of Cas via a processive mechanism . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
An increased association of total Src with Fak and a decreased interaction of p 130 ( CAS ) and p 85 PI3K with Fak were also observed . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
Cellular Src bound to FAK phosphorylates CAS proteins leading to the recruitment of a Crk family adaptor molecule and activation of a small GTPase and c Jun N terminal kinase ( JNK ) promoting membrane protrusion and cell migration . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
FGF 2 induced the activation of Src and subsequent binding to and phosphorylation of Cas in IBE cells , but not in KE 5 15 cells . ^^^
Interacting proteins: P56945 and P12931 Pubmed SVM Score :0.0
CAS was found to bind the SRC 1 interaction domain ( SID ) of CBP via a leucine rich motif in the N terminus of the protein , that is conserved in other SID binding proteins . ^^^