Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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 . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
In contrast , adhesion induced tyrosine phosphorylation of Cas was reduced in cells lacking Src , whereas enhanced phosphorylation of Cas was observed Csk cells , in which Src kinases are activated . ^^^ These results suggest that Src kinases are responsible for the integrin mediated tyrosine phosphorylation of Cas . ^^^ FAK seems not to be necessary for phosphorylation of Cas , but when autophosphorylated , FAK may recruit Src family kinases to phosphorylate Cas . ^^^ Cas was found to form complexes with Src homology 2 ( SH 2 ) domain containing signaling molecules , such as the SH2 / SH3 adapter protein Crk , following integrin induced tyrosine phosphorylation . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
We found that deficiency of c Src but not of other kinases completely abrogated integrin mediated Cas phosphorylation . ^^^ These results suggest that c Src primarily mediates adhesion dependent Cas phosphorylation . ^^^
Interacting proteins: O60716 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: O60716 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 . ^^^ Cas complexes by factors that result in concomitant increase in their phosphotyrosine content , namely cell adhesion and transformation by Src . ^^^ These findings firmly establish a direct interaction between FAK and Cas and demonstrate that Src can influence the subcellular localization of the complex by a tyrosine phosphorylation dependent mechanism . . ^^^
Interacting proteins: O60716 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: O60716 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 . ^^^ From its structure , Cas is deduced to be an ideal substrate for Src family kinases and Abl kinase . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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 . ^^^ Cas was originally cloned as a highly tyrosine phosphorylated protein in cells transformed by 5 Src ( refs 2 , 3 ) or 5 Crk ( ref . 4 ) and has subsequently been implicated in a variety of biological processes including cell adhesion , cell migration , growth factor stimulation , cytokine receptor engagement and bacterial infection . ^^^ Moreover , expression of activated Src in Cas deficient primary fibroblasts did not induce a fully transformed phenotype , possibly owing to insufficient accumulation of actin cytoskeleton in podosomes . ^^^ These findings have defined Cas function in cardiovascular development , actin filament assembly and Src induced transformation . . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
Shear stress stimulation of p 130 ( cas ) tyrosine phosphorylation requires calcium dependent c Src activation . ^^^ 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 . ^^^ Flow mediated activation of c Src , phosphorylation of Cas , and association of Cas with Crk were all inhibited by calcium chelation and pretreatment with the Src family specific tyrosine kinase inhibitor PP 1 . ^^^ To determine the role of c Src in flow stimulated phosphorylation of Cas , we transduced cells with adenovirus encoding kinase inactive Src . ^^^ Calcium dependent activation of c Src and tyrosine phosphorylation of Cas defines a new flow stimulated signal pathway , different from ERK1 / 2 activation . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
The role of SRC CAS interactions in cellular transformation : ectopic expression of the carboxy terminus of CAS inhibits SRC CAS interaction but has no effect on cellular transformation . ^^^ Several lines of evidence indicate that the adapter molecule p130CAS ( crk associated substrate ( CAS ) ) is required for src mediated cellular transformation . ^^^ CAS has been shown to be heavily tyrosine phosphorylated in src transformed cells , and genetic variants of src that are deficient in CAS binding are also unable to mediate cellular transformation . ^^^ In this report , we investigated whether CAS phosphorylation and / or its association with src are required elements of the transformation process . ^^^ Expression of the carboxy terminal src binding domain of CAS in Rat 1 fibroblasts expressing a temperature sensitive allele of 5 src inhibited the formation of src CAS complexes and also inhibited tyrosine phosphorylation of CAS . ^^^
Interacting proteins: O60716 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: O60716 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 ) . ^^^ In contrast , the Src homology 3 domain is required only for the FN induced tyrosine phosphorylation of Cas L and cell migration , but not for CD 3 induced tyrosine phosphorylation or CD 3 plus FN induced cell migration . ^^^
Interacting proteins: O60716 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: O60716 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 . ^^^ A yeast two hybrid screen using the C terminal region of Cas as a bait identified the Src homology 3 ( SH 3 ) domain of the mouse `` nephrocystin ' ' protein orthologous to a human protein whose loss of function leads to the cystic kidney disease familial juvenile nephronophthisis . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
Of the signaling molecules investigated in this study , Src seemed to associate with Cas . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
Protein phosphatase 2A interacts with the Src kinase substrate p 130 ( CAS ) . ^^^ 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 . ^^^ We investigated this interaction in cells expressing a temperature sensitive mutant form of 5 Src . 5 Src activation ( by shifting cells from the nonpermissive to the permissive temperature ) led to an increase in the tyrosine phosphorylation of 5 Src and Cas , as well as in the association between 5 Src and Cas . 5 Src has previously been shown to bind to PP2A and to phosphorylate the catalytic subunit of PP2A , resulting in inhibition of phosphatase activity . ^^^ In contrast , the levels of PP2A that co immunoprecipitated with Cas increased when 5 Src was activated . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
FAK regulates tyrosine phosphorylation of CAS , paxillin , and PYK 2 in cells expressing 5 Src , but is not a critical determinant of 5 Src transformation . ^^^ 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 . ^^^ Despite these effects , FAK does not play an essential role in targeting 5 Src to major cellular substrates including CAS and paxillin . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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 . ^^^ Embryonic fibroblasts lacking Cas demonstrated resistance to Src induced transformation along with impaired actin bundling and cell motility , indicating critical roles of Cas in actin cytoskeleton organization , cell migration , and oncogenesis . ^^^ The C terminal Src binding domain played essential roles in cell migration and membrane localization of Cas , although it was dispensable in the organization of actin stress fibers . ^^^ Furthermore , the Src binding domain was also a prerequisite for Src transformation possibly , because of its crucial role in the phosphorylation of Cas during transformation . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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 . ^^^ Although flow induced Cas phosphorylation was inhibited by kinase inactive Src , PYK 2 activation induced by flow was not inhibited by overexpression of kinase inactive Src . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
We have found that the 120 kD protein is a Crk associated Src substrate , p 130 ( cas ) . ^^^ Specific inhibition of Src family tyrosine kinases attenuated the AII induced p 130 ( cas ) tyrosine phosphorylation . ^^^ These findings strongly suggest that the AII induced p 130 ( cas ) tyrosine phosphorylation might be associated with the signaling pathways of Src family tyrosine kinases , protein kinase C and calcineurin in rat cardiac muscle . . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
PAF exposure induced binding of p 130 ( Cas ) , Src , SHC , and paxillin to FAK . ^^^
Interacting proteins: O60716 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: O60716 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 . ^^^ In this study , we found that the Src homology ( SH ) 3 domain of Cas blocked 5 Src stimulated anchorage independent cell growth , Matrigel invasion , and tumor growth in nude mice . ^^^ Biochemical analysis revealed that the Cas SH 3 domain selectively inhibited 5 Src stimulated activations of AKT and JNK , but not ERK and STAT 3 . ^^^ Attenuation of the AKT pathway by the Cas SH 3 domain rendered 5 Src transformed cells susceptible to apoptosis . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
Src and Cas are essentially but differentially involved in angiotensin 2 stimulated migration of vascular smooth muscle cells via extracellular signal regulated kinase 1 / 2 and c Jun NH 2 terminal kinase activation . ^^^ Here we demonstrated that Ang 2 rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells ( RASMC ) . ^^^ Ang 2 stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1 / 2 and JNK , but not p 38 , were potently inhibited by Src family tyrosine kinase inhibitors , herbimycin A ( HA ) and PP 2 . ^^^ Ang 2 stimulated Src and Cas association , tyrosine phosphorylation of Cas , and activation of ERK1 / 2 and JNK were suppressed in kinase inactive Src ( KI Src ) overexpressed RASMC . ^^^ Ang 2 induced colocalization of Src and Cas and migration were inhibited in both KI Src and DeltaSD Cas overexpressed RASMC . ^^^
Interacting proteins: O60716 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 . ^^^ Using site directed mutagenesis combined with tryptic phosphopeptide mapping , we determined that the ten tyrosines in YXXP motifs 6 15 are the major sites of CAS SD phosphorylation by Src . ^^^ CAS expression enhanced the rate of cell migration into a monolayer wound in a manner dependent on the major sites of Src phosphorylation . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
CAS promotes invasiveness of Src transformed cells . ^^^ CAS ( ' Crk associated substrate ' ) is an Src substrate found at sites of integrin mediated cell adhesion and linked to cell motility and survival . ^^^ In this study , the involvement of CAS in oncogenic transformation was evaluated through analysis of mouse embryo fibroblast populations expressing an activated Src mutant , either in the presence or absence of CAS expression . ^^^ CAS was not found to be a critical determinant of either Src mediated morphologic transformation or anchorage independent growth . ^^^ However , CAS had a profound effect on other aspects of oncogenic Src function . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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 ) . ^^^ As a homolog of the corresponding Src docking domain , the CAS SH 3 domain binds to proline rich sequences ( PxxP ) of its interacting partners that can adopt a polyproline type 2 helix . ^^^
Interacting proteins: O60716 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: O60716 and P12931	Pubmed	SVM Score :0.0
Crk associated substrate ( CAS , p130Cas ) is a major tyrosine phosphorylated protein in cells transformed by 5 crk and 5 src oncogenes . ^^^ We recently reported that reexpression of CAS in CAS deficient mouse embryo fibroblasts transformed by oncogenic Src promoted an invasive phenotype associated with enhanced cell migration through Matrigel , organization of actin into large podosome ring and belt structures , activation of matrix metalloproteinase 2 , and elevated tyrosine phosphorylation of the focal adhesion proteins FAK and paxillin . ^^^ Whereas the presence or absence of CAS did not alter the primary growth of subcutaneous injected Src transformed mouse embryo fibroblasts , CAS expression was required to promote lung metastasis following removal of the primary tumor . ^^^ The substrate domain YxxP tyrosines , the major sites of CAS phosphorylation by Src that mediate interactions with Crk , were found to be critical for promoting both invasive and metastatic properties of the cells . ^^^ The ability of CAS to promote Matrigel invasion , formation of large podosome structures , and tyrosine phosphorylation of Src substrates , including FAK , paxillin , and cortactin , was also strictly dependent on the YxxP tyrosines . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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 . ^^^ JNK activation by FN was enhanced by JSAP 1 , which was suppressed by disrupting the FAK / p130 ( Cas ) pathway by expression of a dominant negative form of p 130 ( Cas ) or by inhibiting Src . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Src family kinases ( SFKs ) bind a specific site in the carboxyl terminal region of Cas and subsequently SFKs phosphorylate progressively the substrate domain in Cas . ^^^ These new molecular data suggest that Cas may regulate activity of Src as a competing ligand to displace intramolecular interactions that occur in SFKs ( between the C terminal tail and the SH 2 domain ) and restrain and down regulate the kinase in an inactive form . . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
SRC uses Cas to suppress Fhl 1 in order to promote nonanchored growth and migration of tumor cells . ^^^ The Src tyrosine kinase phosphorylates specific sites on the focal adhesion adaptor protein Crk associated substrate ( Cas ) to promote nonanchored cell growth and migration . ^^^ We studied the effects of Src and Cas on the expression of > 14 , 000 genes to identify molecular events that underlie these activities . ^^^ We show here that Src phosphorylates Cas to block Fhl 1 expression . ^^^ These data show that Fhl 1 is a tumor suppressor gene that acts downstream of Src and Cas to specifically block anchorage independent cell growth and migration . ^^^
Interacting proteins: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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: O60716 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 . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Recombinant pp 60 ( c src ) efficiently phosphorylated both catenins in vitro , with stoichiometries of 1 . 5 and 2 . 0 mol of phosphate / mol of protein for beta catenin and p 120 catenin , respectively . pp 60 ( c src ) phosphorylation had opposing effects on the affinities of beta catenin and p 120 for the cytosolic domain of E cadherin ; it decreased ( in the case of beta catenin ) or increased ( for p 120 ) catenin / E cadherin binding . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Identification of Src phosphorylation sites in the catenin p120ctn . p 120 catenin ( p 120 ( ctn ) ) interacts with the cytoplasmic tail of cadherins and is thought to regulate cadherin clustering during formation of adherens junctions . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Phosphorylated `` optimal Src substrate ' ' AEEEIpYGEFEA ( where pY is phosphotyrosine ) and a phosphopeptide corresponding to a recently identified Src phosphorylation site in p 120 catenin , DDLDpY ( 296 ) GMMSD , were excellent SHP 1 substrates . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Although originally identified as a Src substrate , p 120 catenin ( p 120 ) is now known to regulate cell cell adhesion through its interaction with the cytoplasmic tail of classical and type 2 cadherins . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Studies by immunoprecipitation revealed that Fer kinase associated with N cadherin , gamma catenin , p120ctn , c Src ( a putative PTK and the product of the transforming , sarcoma inducing gene of Rous sarcoma virus ) , Rab 8 ( a GTPase ) , actin , vimentin , but not E cadherin , afadin , nectin 3 , and integrin beta 1 , suggesting Fer kinase associates not only with the actin based cell cell AJ structures , such as the N cadherin / catenin complex ( but not the alpha6beta1 integrin / laminin and the afadin / nectin complex ) , but also with intermediate filament based cell cell desmosomes . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
In the case where the Src MDCK cells were cultivated at 35 degrees C and shifted for short time periods to 40 . 5 degrees C , cadherin rapidly returned to lateral membranes , whereas actin and p120ctn followed hours afterward . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Furthermore , we demonstrate that the E cadherin endocytosis dependent activation of Rap 1 is associated with and controlled by an increased Src kinase activity , and is paralleled by the colocalization of Rap 1 and E cadherin at the perinuclear Rab 11 positive recycling endosome compartment , and the association of Rap 1 with a subset of E cadherin catenin complexes that does not contain p120ctn . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Treatment with the specific src kinase inhibitor PP 1 increased E cadherin expression in IGtM 87 and SKOV 3 cells and enhanced membrane localization of both E cadherin and p120ctn . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Identification of a new catenin : the tyrosine kinase substrate p120cas associates with E cadherin complexes . p120cas is a tyrosine kinase substrate implicated in ligand induced receptor signaling through the epidermal growth factor , platelet derived growth factor , and colony stimulating factor receptors and in cell transformation by Src . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Similarily , p120cas , the Arm domain containing src substrate , also binds to cadherins and becomes tyrosine phosphorylated in response to a variety of stimuli . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
The catenin p 120 ( ctn ) ( formerly p120cas ) was first identified as a src and receptor protein tyrosine kinase substrate and later shown to interact directly with cadherins . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
Expression patterns of the novel catenin p120cas in gastrointestinal cancers . p120cas is involved in signal transduction upon src or growth factor stimulation as well as in E cadherin mediated cell adhesion and may play an important role in carcinogenesis . ^^^
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
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Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: O60716 and P12931	Pubmed	SVM Score :0.0
NA