Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.51792322
Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH 2 domain mediated association of the GRB 2 adaptor protein and the c Src protein tyrosine kinase ( PTK ) with FAK in vivo , and also results in activation of mitogen activated protein kinase ( MAPK ) . 0.51792322^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.68026174
We also showed potentially direct interaction of FAK with 5 Src in vivo using the yeast two hybrid system . 0.68026174^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.51117736
We also detected a basal constitutive association of Src kinase with FAK in HER 14 cells . 0.51117736^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.60362003
Expression of merlin attenuated FAK phosphorylation at the critical phosphorylation site Tyr 397 and disrupted the interaction of FAK with its binding partners Src and p 85 , the regulatory subunit of phosphatidylinositol 3 kinase . 0.60362003^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.55657877
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 . 0.55657877^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.5861455
In this report , we present evidence for the stable association of two Src family kinases ( pp60src and pp59fyn ) with tyrosine phosphorylated forms of a focal adhesion associated protein tyrosine kinase , pp125FAK . 0.5861455^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.52800081
Thrombin stimulates association of src homology domain containing adaptor protein Nck with pp125FAK . 0.52800081^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Neuropeptide stimulated tyrosine phosphorylation of specific components in Swiss 3T3 cells was investigated using monoclonal antibodies directed against the src transformation associated substrates p 125 focal adhesion kinase ( FAK ) , a novel type of cytosolic tyrosine kinase , and p 130 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The focal adhesion kinase ( FAK ) has been implicated in integrin mediated signaling events and in the mechanism of cell transformation by the 5 Src and 5 Crk oncoproteins . ^^^ 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 . ^^^ The Src family kinase Fyn , whose Src homology 2 ( SH 2 ) domain binds to the major FAK autophosphorylation site ( tyrosine 397 ) , was also identified in the two hybrid screen . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The identification of Tyr 397 as a major site for FAK autophosphorylation provides one of the first examples of a cellular protein containing a high affinity binding site for a Src family kinase SH 2 domain . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) is a widely expressed nonreceptor protein tyrosine kinase implicated in integrin mediated signal transduction pathways and in the process of oncogenic transformation by 5 Src . ^^^ To help elucidate the role of FAK phosphorylation in signal transduction events , we used a tryptic phosphopeptide mapping approach to identify tyrosine sites of phosphorylation responsive to both cell adhesion and Src transformation . ^^^ Our results indicate that phosphorylation of FAK by Src ( or other Src family kinases ) is an important step in the formation of an active signaling complex . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Several tyrosine kinases , including Src family kinases , Syk and FAK , have been implicated in these phosphorylation events . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To gain insight into FAK function , we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK cooperation in development of CD4+CD8+ thymocytes . p59fyn is an Src family nonreceptor tyrosine kinase that has been suggested to play an important role in T cell development and function . p125FAK is a unique nonreceptor tyrosine kinase and has been known to respond to integrin extracellular matrix interactions . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This effect required the autophosphorylation site of FAK , which is a binding site for Src family kinases . ^^^ FAK seems not to be necessary for phosphorylation of Cas , but when autophosphorylated , FAK may recruit Src family kinases to phosphorylate Cas . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Immunoprecipitation experiments with specific antibodies against potential candidate proteins in the molecular mass range around 130kDa revealed positive results for the focal adhesion kinase FAK and the p 130 Src substrate while negative results were obtained for the GTPase activating protein GAP , the phospholipase C gamma 1 , the Janus kinase JAK 1 and vinculin . ^^^ The data suggest that the tyrosine phosphorylation of FAK and the pl 30 Src substrate might be involved in the B 2 kinin receptor signalling cascade . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These data suggest that RAFTK is a novel member of the FAK family , that it localizes to focal adhesion like structures in CMK megakaryocytic cells , that it participates in integrinmediated signaling pathways in megakaryocytes , and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb 2 via SH 2 phosphotyrosine interactions . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
During the early stage of neurogenesis , FAK is phosphorylated , shows multiple isoforms , and interacts with the proto oncogenes , src , fyn , and lyn . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We showed previously that the c Src nonreceptor PTK and the Grb 2 SH2 / SH3 adaptor protein bound directly to FAK after fibronectin stimulation ( D . ^^^ Here , we present evidence that c Src association with FAK is required for Grb 2 binding to FAK . ^^^ In vitro , c Src phosphorylated FAK Tyr 925 in a glutathione S transferase FAK C terminal domain fusion protein , whereas FAK did not . ^^^ Using epitope tagged FAK constructs , transiently expressed in human 293 cells , we determined the effect of site directed mutations on c Src and Grb 2 binding to FAK . ^^^ Mutation of FAK Tyr 925 disrupted Grb 2 binding , whereas mutation of the c Src binding site on FAK ( Tyr 397 ) disrupted both c Src and Grb 2 binding to FAK in vivo . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We also find that the wild type and the kinase defective FAK were associated with Src and Fyn in CHO cells whereas the F 397 mutant was not . ^^^ They also provide evidence for the functional significance of FAK / Src complex formation in vivo . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Paxillin is a 68 kD focal adhesion phosphoprotein that interacts with several proteins including members of the src family of tyrosine kinases , the transforming protein 5 crk , and the cytoskeletal proteins vinculin and the tyrosine kinase , focal adhesion kinase ( FAK ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
RAFTK has an overall 48 % amino acid homology to p 125 ( FAK ) and contains a kinase domain but lacks a transmembrane region , myristylation sites , and Src homology region 2 and 3 domains . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Full activation of FAK appears to require additional phosphorylation by the associated Src family kinases . ^^^ Previously identified Src sites include catalytic domain tyrosines 576 and 577 , important for maximal FAK kinase activity , and tyrosine 925 , which permits an SH 2 mediated association with Grb 2 . ^^^ Here we report that tyrosine 861 is the major Src site in the carboxyl terminal domain of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We have examined the function of the epidermal growth factor ( EGF ) receptor , c Src and focal adhesion kinase ( FAK ) in the progression of colon cancer using an in vitro progression model . ^^^ We have shown that both EGF receptor and FAK protein levels were elevated in the carcinoma cells as compared to the adenoma cells , while the expression and activity of c Src were unaltered during the adenoma to carcinoma transition . ^^^ This increased motility was accompanied by an EGF induced increase in c Src kinase activity , relocalisation of c Src to the cell periphery and phosphorylation of FAK in the carcinoma cells but not in the adenoma cells . ^^^ This suggests that c Src plays a role in the biological behaviour of colonic carcinoma cells induced by migratory factors such as EGF , perhaps acting in conjunction with FAK to regulate focal adhesion turnover and tumour cell motility . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Analysis revealed cytoskeletal association of c Src , FAK , and beta 3 integrin , but no Fyn , in the pressure overloaded right ventricle . ^^^
Interacting proteins: Q658W2 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 . ^^^ Requirements for Src kinase activity and FAK proline rich motifs . ^^^ 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 . ^^^ FAK kinase domain tyrosines 576 and 577 are also required , suggesting that direct phosphorylation of these sites by Src may influence the solubility and / or stability of the complex . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins , including 5 Src . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
NCAM 140 interacts with the focal adhesion kinase p 125 ( fak ) and the SRC related tyrosine kinase p 59 ( fyn ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Exciting recent data show that angiotensin 2 directly stimulates tyrosine kinases , including pp 60 ( c src ) kinase ( c Src ) , focal adhesion kinase ( FAK ) , and Janus kinases ( JAK 2 and TYK 2 ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These can be divided into nine families : Abl , Fes / Fer , Syk / Zap70 , Jak , Tec , Fak , Ack , Src , and Csk . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK autophosphorylation at Tyr 397 promotes Src homology 2 ( SH 2 ) domain binding of Src family PTKs , and c Src phosphorylation of FAK at Tyr 925 creates an SH 2 binding site for the Grb 2 SH2 SH 3 adaptor protein . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Recent data show that angiotensin 2 stimulates not only cytoplasmic tyrosine kinases including c Src , focal adhesion kinase ( FAK ) , and Janus kinases ( JAK 2 and TYK 2 ) , but also may transactivate receptor tyrosine kinases such as Axl and PDGF by as yet undefined autocrine / paracrine mechanisms . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Associated with DIGEM , many signal transducer molecules such as c Src , FAK , and the low molecular weight G proteins Rho A and H Ras were also found . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here it is reported that ET 1 promotes the formation of stress fibers and focal adhesions and the tyrosine phosphorylation of focal adhesion kinase ( FAK ) and paxillin , as well as Src activation and association of phosphorylated FAK with Grb 2 . ^^^ Pretreatment of astrocytes with cytochalasin D or C 3 transferase , which inhibits actin polymerization or Rho activity , respectively , prevented the activation / phosphorylation of Src , FAK , and paxillin after ET 1 stimulation ; by contrast , the ERK pathway was not significantly affected . ^^^ This differential activation of FAK / Src and ERK pathways was also observed with astrocytes 10 and 60 min after replating on poly L ornithine precoated dishes . ^^^ Collectively , these findings indicate that activation of FAK and Src is dependent on actin cytoskeleton integrity , Rho activation , and adhesion to extracellular matrix , whereas ERK activation is independent of these intracellular events and seems to correlate with activation of the newly identified protein tyrosine kinase PYK 2 . ^^^ This study provides a demonstration of Rho and adhesion dependent activation of FAK / Src , which collaborates with adhesion independent activation of PYK2 / ERK for DNA synthesis in ET 1 stimulated astrocytes . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To investigate the mechanisms by which FAK , c Src , and Grb 2 function in FN stimulated signaling events to ERK 2 , we expressed wild type and mutant forms of FAK in human 293 epithelial cells by transient transfection . ^^^ FN stimulated c Src PTK activity was enhanced by wild type FAK expression , whereas FN stimulated activation of ERK 2 was blocked by expression of the c Src binding site Phe 397 mutant of FAK . ^^^ The inhibitory effects of Tyr 397 FAK expression show that FAK mediated association and activation of c Src is essential for maximal signaling to ERK 2 . ^^^ Moreover , multiple signaling pathways are activated upon the formation of an FAK . c Src complex , and several of these can lead to Ras dependent ERK 2 mitogen activated protein kinase activation . . ^^^ Focal adhesion kinase ( FAK ) associates with integrin receptors , and FN stimulated phosphorylation of FAK at Tyr 397 and Tyr 925 promotes the binding of Src family PTKs and Grb 2 , respectively . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Important candidates for these changes include members of the c Src and FAK families . c Src is now considered to be a component of the focal adhesion complex and regulate focal adhesion formation and / or cytoskeletal rearrangement . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Activation and autophosphorylation of FAK lead to its binding to a number of intracellular signaling molecules , including Src , Grb 2 and PI 3 kinase . ^^^ FAK / Src association activates both kinases , which act on the potential substrates tensin , paxillin and p130cas . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Autophosphorylation of FAK at Y 397 leads to its association with Src , resulting in activation of both kinases . ^^^ The activated FAK / Src complex acts on potential substrates tensin , paxillin and p130cas . ^^^ Src association with FAK may also lead to its phosphorylation of other sites on FAK , including a binding site for Grb 2 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We show that a consensus Src SH 3 binding site residing upstream of the Src SH 2 binding site in FAK can function as a ligand for the Src SH 3 domain . ^^^ Surface plasmon resonance experiments indicate that a FAK peptide containing both the Src SH 2 and SH 3 binding sites exhibits increased affinity for Src . ^^^ A FAK mutant ( FAKPro 2 ) with substitutions destroying the SH 3 binding site shows reduced binding to Src in vivo . ^^^ These observations suggest that an SH 3 mediated interaction between Src like kinases and FAK may be important for complex formation and downstream signaling in vivo . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The adhesion of platelets to vWf resulted in dramatic actin filament reorganization , as assessed by immunofluorescence with fluorescein isothiocyanate conjugated phalloidin , and the cytoskeletal recruitment of various structural proteins ( talin and integrin alphaIIbbeta 3 ) and signaling enzymes ( pp60c src , focal adhesion kinase ( FAK ) , phosphatidylinositol 3 kinase ( PI 3 kinase ) , and protein tyrosine phosphatase ( PTP ) 1B ) . ^^^ The activation of calpain in both spreading and aggregated platelets resulted in a substantial decrease in the level of tyrosine phosphorylation of multiple platelet proteins and was associated with a 50 80 % reduction in the amount of cytoskeletal associated talin , integrin alphaIIbbeta 3 , PI 3 kinase , FAK , pp 60 ( c ) src , and PTP 1B . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The presence of the various exons did not alter the interaction of FAK with c Src , n Src , or Fyn . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Inhibition of cell spreading by expression of the C terminal domain of focal adhesion kinase ( FAK ) is rescued by coexpression of Src or catalytically inactive FAK : a role for paxillin tyrosine phosphorylation . pp125FAK is a tyrosine kinase that appears to regulate the assembly of focal adhesions and thereby promotes cell spreading on the extracellular matrix . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Immunoprecipitations with selective monoclonal antibodies demonstrated that both chrysotile and crocidolite asbestos increase kinase activities associated with p 60 Src or p 120 focal adhesion kinase ( FAK ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
PKC depletion did not alter Ang 2 dependent tyrosine phosphorylation or activity of p 125 ( FAK ) , CADTK , Fyn or Src , but PKC depletion or incubation with GF109203X resulted in Ang 2 dependent EGF receptor tyrosine phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Previously we have demonstrated that focal adhesion kinase ( FAK ) promoted migration on fibronectin ( FN ) by its overexpression in CHO cells is dependent on FAK autophosphorylation at Y 397 and subsequent binding of Src to this site . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Three of these proteins were identified as Src , paxillin , and focal adhesion kinase ( FAK ) , all of which show an increase in their tyrosine phosphate levels with increasing density . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In rabbit colonic muscularis mucosae cells , tyrosine phosphorylated proteins of approximately 60 and 125 kDa were observed in immunoblots using an anti phosphotyrosine antibody and were identified as c Src and focal adhesion kinase ( FAK ) by immunoblotting with specific antibodies . ^^^ FAK co immunoprecipitated with c Src , and the phosphorylation of the c Src . ^^^ In whole cell patch clamp studies , intracellular dialysis of a Src substrate peptide and anti c Src and anti FAK antibodies suppressed Ca2+ currents by 60 , 62 , and 43 % , respectively . ^^^ Co dialysis of anti c Src and anti FAK antibodies inhibited Ca2+ currents ( 63 % ) equivalent to dialysis with the anti c Src antibody alone . ^^^ PDGF BB enhanced Ca2+ currents by 43 % , which was abolished by the anti c Src and anti FAK antibodies . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We now report that the adhesion process is based essentially on a glycosphingolipid enriched microdomain ( GEM ) at the B 16 cell surface , since > 90 % of GM 3 present in the original cells is found in GEM , and GEM is also enriched in several signal transducer molecules , e . g . c Src , Ras , Rho , and focal adhesion kinase ( FAK ) . ^^^ A close association of GM 3 with c Src , Rho , and FAK was indicated by co immunoprecipitation of GM 3 present in GEM by anti GM 3 monoclonal antibody DH 2 , followed by Western blotting with antibodies directed to these transducer molecules . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although MC3T3 E 1 cells express much more Fak than Pyk 2 , Src preferentially associated with Pyk 2 . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Our results also suggest that the activation of Src upon HGF stimulation is likely to be one , if not the only , of the mechanisms responsible for the HGF induced tyrosine phosphorylation of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In this study , we show that the nonreceptor protein tyrosine kinases ( PTKs ) c Src and focal adhesion kinase ( FAK ) can be independently activated after fibronectin ( FN ) stimulation and that their combined activity promotes signaling to extracellular signal regulated kinase 2 ( ERK 2 ) / MAP kinase through multiple pathways upstream of Ras . ^^^ FN stimulation of NIH 3T3 fibroblasts promotes c Src and FAK association in the Triton insoluble cell fraction , and the time course of FN stimulated ERK 2 activation paralleled that of Grb 2 binding to FAK at Tyr 925 and Grb 2 binding to Shc . ^^^ Cytochalasin D treatment of fibroblasts inhibited FN induced FAK in vitro kinase activity and signaling to ERK 2 , but it only partially inhibited c Src activation . ^^^ Treatment of fibroblasts with protein kinase C inhibitors or with the PTK inhibitor herbimycin A or PP 1 resulted in reduced Src PTK activity , no Grb 2 binding to FAK , and lowered levels of ERK 2 activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Roles of Fak and Src family kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Lysophosphatidic acid induced association of SHP 2 with SHPS 1 : roles of RHO , FAK , and a SRC family kinase . ^^^ These results indicate that LPA induced tyrosine phosphorylation of SHPS 1 and its association with SHP 2 may be mediated by a RHO dependent pathway that includes FAK and a SRC family kinase . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Addition of the selective Src inhibitor pyrazolopyrimidine directly to the in vitro kinase assay potently inhibited Src kinase activity induced by bombesin but did not affect the kinase activity of FAK measured by autophosphorylation or by synthetic substrate phosphorylation in paralell assays . ^^^ In addition , Src activity was not detected in FAK immunoprecipitates using an optimal Src peptide substrate . ^^^ Thus , agonist induced tyrosine kinase activity measured in FAK immunoprecipitates is mediated by FAK activation rather than by co immunoprecipitating Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Concomitant with focal complex formation , we observed some phosphorylation of the focal adhesion kinase ( FAK ) and Src , which occurred independently of Rho family GTPases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , regulated association of Src SH 2 domain with FAK and paxillin during cell attachment and detachment on fibronectin was disrupted in Shp 2 mutant cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Consistent with these data , CD 146 associates with p 59 ( fyn ) , a Src family kinase known to phosphorylate p 125 ( FAK ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
It is a multi domain adapter protein capable of interacting with several structural and signaling proteins including vinculin , FAK , PYK 2 , Src and Crk . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
It is well established that Tyr 397 is the FAK autophosphorylation site and Tyr 407 , 576 / 577 , 861 , and 925 are the sites on murine FAK that are mediated by Src family kinases . ^^^ Thus , we conclude that Src mediated FAK phosphorylation is regulated by a tyrosine phosphatase ( s ) and may be of physioligical significance . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Specifically , the autophosphorylation site of FAK , which is a reported site of c Src kinase binding , is required for bacterial internalization , as overexpression of a derivative lacking the autophosphorylation site had a dominant interfering effect as well . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
PTPalpha expression also led to increased association of Src kinase with the integrin associated focal adhesion kinase , pp 125 ( FAK ) . ^^^ In addition , paxillin , a Src and / or pp 125 ( FAK ) substrate , displayed increased levels of tyrosine phosphorylation in PTPalpha expressing cells and was associated with elevated amounts of Csk . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
One of the major proteins implicated in integrin signaling is pp 125 ( FAK ) , a cytosolic tyrosine kinase , which upon integrin engagement becomes tyrosine phosphorylated and subsequently binds to c Src . ^^^ Insulin receptor substrate 1 as a signaling molecule for focal adhesion kinase pp 125 ( FAK ) and pp 60 ( src ) . ^^^ When IRS 1 was expressed in 293 cells together with pp 125 ( FAK ) or Src , we found extensive IRS 1 tyrosine phosphorylation . ^^^ In pp 125 ( FAK ) expressing cells , this was concomitant with increased association of IRS 1 with Src homology 2 containing proteins such as growth factor receptor bound protein 2 , phosphatidylinositol ( PI ) 3 kinase p85alpha subunit , and Src homology 2 containing protein tyrosine phosphatase 2 . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Biochemical analyses indicated that FAK mutant DeltaC 14 was mislocalized and functioned as a dominant negative mutant by competing with endogenous FAK in focal contacts for binding signaling molecules such as Src and Fyn , resulting in a decreases of Erk activation in cell adhesion . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Overexpression of both wild type ( WT ) and kinase inactive ( Ala 457 ) , but not the autophosphorylation site mutant ( Phe 402 ) Pyk 2 , enhanced endogenous FN stimulated c Src in vitro kinase activity in FAK cells , but only WT Pyk 2 overexpression enhanced FN stimulated activation of co transfected ERK 2 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
On the other hand , overexpression of Csk DeltaK induced tyrosine phosphorylation of cellular proteins , including the paxillin and focal adhesion kinase ( FAK ) and enhanced to some extent the cytoskeletal organization and the rate of cell spreading on fibronectin , indicating that Src or its relatives was functionally activated in the cells . ^^^ These findings suggest that Csk regulates Src family tyrosine kinases that play essential roles in the regulation of cell adhesion via a FAK dependent mechanism and that the tyrosine phosphorylation of paxillin alone may not be sufficient for the regulation of the cell adhesion mechanism in astrocytes . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Tyrosine kinases activated by AngII include c Src , focal adhesion kinase ( FAK ) , Pyk 2 ( CADTK ) , Janus kinases ( JAK 2 and TYK 2 ) , and the receptor tyrosine kinases Ax 1 , epidermal growth factor , and platelet derived growth factor . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Pertussis toxin insensitive G proteins , most likely from G alpha 12 class , cause the activation of several cytoplasmic protein tyrosine kinases [ Src , Pyk 2 ( proline rich tyrosine kinase 2 ) , and Fak ( focal adhesion kinase ) ] . ^^^ Activation of Erks can lead to osteoblast proliferation and differentiation , while activation of Src , Pyk 2 and Fak can modulate the adhesion properties of osteoblasts . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
In addition to previously identified involvement of phosphatidylinositol 3 kinase ( PI 3 K ) , JNK , and MAPK , we found that FAK , c Src , and AKT are rapidly and transiently activated by MSP . ^^^ FAK , MAPK , and c Src are involved in MSP induced cell proliferation . ^^^ FAK also regulates MSP induced cell growth , but via a path different from c Src / MAPK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here we report that depletion of caveolin by antisense methodology in kidney 293 cells disrupts the association of Src kinases with beta 1 integrins resulting in loss of focal adhesion sites , ligand induced focal adhesion kinase ( FAK ) phosphorylation , and adhesion . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The differentiation of Caco 2 cells was associated with : 1 ) down regulation of beta 1 integrin expression at the mRNA and protein levels ; 2 ) increased FAK expression together with decreased FAK autophosphorylation ; 3 ) decreased FAK ' s ability to associate with PI 3 kinase and pp60c src ; and 4 ) increased MAP kinase expression along with decreased MAP activity . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
The discrepancy in extent of integrin dysfunction between murine and human platelet models may be due to lack of specificity of piceatannol , because this compound inhibited the activity of Src and FAK as well as Syk and also reduced tyrosine phosphorylation of multiple platelet proteins . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This residue was known to serve as a binding site for both Src and phosphatidylinositol 3 kinase ( PI3K ) , implying that either one or both are required for FAK to promote cell migration . ^^^ Furthermore , a FAK mutant capable of binding Src but not PI3K was generated by a substitution of Asp residue 395 with Ala . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Fibronectin induced tyrosine phosphorylation of focal adhesion proteins , including the focal adhesion kinase FAK , was nearly eliminated in the absence of Src , Yes and Fyn . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The compound was selective toward other protein kinases : the Src IC 50 value was lower than those for Cdc 2 ( > 500 fold ) , epidermal growth factor ( EGF ) receptor ( 7 . 5 fold ) , and vascular endothelial growth factor receptor ( > 50 fold ) , and for 5 Abl ( 15 fold ) and focal adhesion kinase ( Fak ) ( > 25 fold ) . ^^^ To measure the inhibition of cellular Src activity , we identified the major tyrosine phosphorylated proteins in an Src overexpressing cell line IC8 . 1 as Src , Fak , and paxillin . ^^^ CGP 77675 potently inhibited tyrosine phosphorylation of the Src substrates Fak and paxillin , but had much less effect on Src ( IC 50 values 0 . 3 , 0 . 5 , and 5 . 7 micromol / L ) . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins GRB 2 , Shc , and nonreceptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In differentiating EC , FGF 2 induces complex formation between Src and focal adhesion kinase ( FAK ) . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Tyr 576 and Tyr 577 lie in the putative activation loop of the kinase domain , and FAK catalytic activity may be elevated through phosphorylation of these residues by associated Src family kinase . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
In particular , integrins regulate many protein tyrosine kinases and phosphatases , such as FAK and Src , to coordinate many of the cell processes mentioned above . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To check this hypothesis , phosphorylation of the FAK and paxillin proteins , involved in signal transduction pathways and known as src protein substrates , was tested . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cat proteins are tyrosine phosphorylated when co expressed in cells with the focal adhesion kinase Fak and Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here evidence is presented that the FAK autophosphorylation site Tyr 397 mediates a direct interaction with the C terminal Src homology 2 domain of phospholipase C ( PLC ) gamma 1 and that this is required for both adhesion dependent association of the two molecules and increased inositol phosphate production in mouse embryo fibroblasts . ^^^ These observations suggest a role for FAK in recruiting PLC gamma 1 to the plasma membrane at sites of cell matrix adhesion and there promoting its enzymatic activity , possibly by releasing the repression caused by intramolecular interactions of the PLC gamma 1 Src homology domains and / or by positioning it for phosphorylation by associated Src family kinases . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here , we show that hypoxia induced tyrosine phosphorylation of p 125 ( FAK ) and paxillin and that hypoxia induced activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins Shc and GRB 2 , and non receptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cytoskeletal reorganization leads to induction of the urokinase type plasminogen activator gene by activating FAK and Src and subsequently the Ras / Erk signaling pathway . ^^^ Changes in cell morphology triggered by extracellular signals are often mediated by integrin associated proteins , such as focal adhesion kinase ( FAK ) and Src . ^^^ We found that CSR induced the activation of FAK and Src and the association of FAK and Shc , a signaling molecule linking growth factor receptor tyrosine kinase and Grb 2 . ^^^ Furthermore , expression of either FRNK , a kinase minus FAK like molecule acting as a dominant negative FAK , or a dominant negative Src suppressed CSR induced uPA gene promoter activation . ^^^ These results suggest that cells respond to a morphology change , using the cytoskeleton as a sensor , by activating FAK and Src and subsequently the Ras / Erk signaling pathway . . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Stimulation of quiescent Swiss 3T3 cells with bombesin induces a rapid increase in the formation of complexes between focal adhesion kinase ( FAK ) and Src family members , which can be extracted with a buffer containing Triton , deoxycholate , and SDS but not with a buffer containing Triton alone . ^^^ An increase in complex formation between FAK and Src in response to bombesin could be detected within 1 min , reached a maximum after 10 min , and declined toward base line levels after 60 min of bombesin treatment . ^^^ Bradykinin , endothelin , and lysophosphatidic acid also stimulated FAK Src complex formation . ^^^ Bombesin stimulated FAK / Src association through a Ca ( 2+ ) and phosphatidylinositol 3 ' kinase independent pathway that requires the integrity of the actin filament network and is partly dependent on functional protein kinase C . ^^^ Treatment with the selective Src kinase inhibitor PP 2 inhibited both FAK activation and phosphorylation of FAK at Tyr ( 577 ) induced by bombesin in intact cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These results suggest that paxillin must bind FAK for maximal phosphorylation in response to cell adhesion and that FAK may function to direct tyrosine phosphorylation of paxillin in the process of transformation by the src oncogene . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Phosphorylation of FAK Tyr 397 creates a binding site for Src family kinases , and phosphorylation of FAK Tyr 576 / Tyr 577 in the kinase domain activation loop enhances catalytic activity . ^^^ Using novel phosphospecific antibody reagents , we show that FAK activation loop phosphorylation is significantly elevated in cells expressing activated Src and is an early event following cell adhesion to fibronectin . ^^^ Our findings support a model for reciprocal activation of FAK and Src family kinases and suggest that FAK / Src signaling may occur during both focal adhesion assembly and turnover . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These observations indicate that DSGG is clustered in RCC , as typified by TOS 1 cells , to form a microdomain in which it is closely associated with c Src , Rho A , and FAK , and may constitute a functional unit as has been observed for GM 3 with transducer molecules in B 16 cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We show that simultaneous overexpression of FAK and pp 60 ( c src ) or p 59 ( fyn ) results in the enhancement of the tyrosine phosphorylation of a limited number of cellular substrates , including paxillin . ^^^ FAK mutants defective for Src binding or focal adhesion targeting fail to cooperate with pp 60 ( c src ) or p 59 ( fyn ) to induce paxillin phosphorylation , whereas catalytically defective FAK mutants can direct paxillin phosphorylation . ^^^ The negative regulatory site of pp 60 ( c src ) is hypophosphorylated when in complex with FAK , and coexpression with FAK leads to a redistribution of pp 60 ( c src ) from a diffuse cellular location to focal adhesions . ^^^ A FAK mutant defective for Src binding does not effectively induce the translocation of pp 60 ( c src ) to focal adhesions . ^^^ Tyrosine phosphorylation of focal adhesion kinase ( FAK ) creates a high affinity binding site for the src homology 2 domain of the Src family of tyrosine kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) and paxillin are known to form a complex with c Src at the focal contacts and to participate in the integrin mediated signal transduction as c Src substrates . ^^^ These findings suggest that tyrosine phosphorylation of the endometrial paxillin and FAK is not tightly regulated by the kinase activity of c Src during in vitro decidualization . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Mouse melanoma B 16 cells are characterized by a high concentration of GM 3 ganglioside , which has been identified as a melanoma associated antigen and is present as a clustered microdomain organized with major signal transducers , c Src , small G protein ( Rho A ) , and focal adhesion kinase ( FAK ) , to form a `` glycosphingolipid signaling domain ' ' or `` glycosignaling domain ' ' ( GSD ) separable from cholesterol and caveolin enriched microdomain , `` caveolae . ' ' Cholesterol binding reagents , filipin and nystatin , disrupt the structure and function of caveolae , but have no effect on GSD function [ Iwabuchi , K . , et al . ( 1998 ) J . ^^^ Substitution of the Sph amino group with a chloroacetyl or N , N dimethyl group strongly reduced the inhibitory effect of sialyl alpha 2 > 1 Sph on GM 3 dependent adhesion , FAK , and c Src response . ^^^ Analogues with N substitution of Sph in sialyl alpha 2 > 1 Sph , other lyso phospholipids , and galactosyl or lactosyl Sph did not block such adhesion , coupled with activation of c Src and FAK . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To address this problem , we transfected MCF 7 cells to express the noncatalytic carboxylterminal domain of focal adhesion kinase ( FAK ) , FAK ( Y397F ) , kinase defective c Src , or Shc FFF , all of which express dominant negative activity . ^^^ Both activities were rescued by co transfecting the cells to express constitutively active MEK 1 , indicating that FAK , c Src , and Shc are upstream of MEK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
HFS enhanced association of the src family kinases fyn and c src with an approximately 120 kDa tyrosine phosphorylated component containing the focal adhesion kinase ( FAK ) and its homologue PYK 2 . ^^^ Association of fyn with FAK and of c src with PYK 2 was increased following the HFS . ^^^ These results suggest that fyn and c src are involved in distinct signaling pathways and provide evidence for activation of FAK and PYK 2 following synaptic stimulation inducing LTP in vitro . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
GM 3 ganglioside at the surface of mouse melanoma B 16 cells is clustered and organized with signal transducer molecules c Src , Rho A , and focal adhesion kinase ( FAK ) to form a membrane unit separable from caveolae , which are enriched in cholesterol and caveolin but do not contain GM 3 or the above three signal transducers . ^^^ The GM 3 enriched membrane units are involved in GM 3 dependent cell adhesion coupled with activation of c Src , Rho A , and FAK and are termed the `` glycosphingolipid signaling domain ' ' or the `` glycosignaling domain ' ' ( GSD ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We demonstrate that FAK phosphorylation induced by integrins during focal adhesion assembly differs from that induced by activation of a temperature sensitive 5 Src , which is associated with focal adhesion turnover and transformation . ^^^ Specifically , although 5 Src induces tyrosine phosphorylation of FAK , there is no detectable phosphorylation of Tyr ( 397 ) . ^^^ Our mutational analysis further indicates that the binding of 5 Src to Tyr ( 397 ) of FAK in its phosphorylated form , which is normally mediated , at least in part , by the SH 2 domain of Src , is not essential for 5 Src induced cell transformation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cross linking demonstrated that FGF 2 / HSGAGB primarily activated FGFR 1 , which in turn up regulated the activity of mitogen activated protein kinase ; in contrast , FGF 1 / HSGAGA led to the phosphorylation of equal proportions of both FGFR 1 and FGFR 2 , which in turn led to the up regulation of Src and p 125 ( FAK ) . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
We also found that Grb 7 could be phosphorylated by FAK , which was dependent on the FAK kinase activity but not the presence of the Src family kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To explore the cellular mechanism whereby TNF alpha regulates phosphorylation of FAK in the liver , we measured c Src kinase activity and the abundance of 3 major protein tyrosine phosphatases ( PTPs ) ( PTP 1B , leukocyte antigen related tyrosine phosphatase [ LAR ] , and src homology 2 domain containing protein tyrosine phosphatase [ SHPTP 2 ] ) in liver homogenates from obese Zucker rats after TNF alpha blockade . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
This suggested that they may inhibit Erk activation in an analogous manner as the mislocalized FAK mutant ( & Dgr ; ) C 14 described previously by competing with endogenous FAK for binding signaling molecules such as Src and Fyn . ^^^ This model is further supported by an inhibition of endogenous FAK association with active Src by Pyk 2 and FPhy 2 and a partial rescue by FAK of Pyk 2 mediated cell cycle inhibition . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although the SH 3 domain of 5 Src is also necessary for its association with focal adhesion kinase ( FAK ) , which is often considered a likely candidate mediator of focal adhesion targeting via its carboxy terminal targeting sequence , we show here that binding to FAK is not essential for the targeting of 5 Src to focal adhesions . ^^^
Interacting proteins: Q658W2 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 . ^^^ Whereas cardiocytes under both conditions showed RGD stimulated ERK1 / 2 activation , only collagen embedded cells exhibited cytoskeletal assembly of FAK , c Src , Nck , and Shc . ^^^ 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 . ^^^ Therefore , c Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here we concentrate on three non receptor kinases : Src , focal adhesion kinase ( FAK ) and phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , E4orf4 dramatically inhibited the ability of FAK and c src to cooperate in induction of tyrosine phosphorylation of cellular substrates , suggesting that E4orf4 can interfere with the formation of a signaling complex at focal adhesion sites . ^^^ Evidence that E4orf4 can associate with and modulate Src family kinase activity , inhibiting Src dependent phosphorylation of focal adhesion kinase ( FAK ) and paxillin while increasing phosphorylation of cortactin and some other cellular proteins , is presented . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Expression of FRNK , but not a point mutant of FRNK ( FRNK L1034S ) , disrupted the formation of a complex containing both FAK and the activated PDGF beta receptor and resulted in reduced tyrosine phosphorylation of endogenous FAK at the Tyr 397 binding site for Src family PTKs . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These events were paralleled by c Src activation and binding to Fak and by an association of Grb 2 and p 85 subunit of phosphatidylinositol 3 kinase with Fak . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Consistent with the invasion results , overexpression of FRNK , a kinase negative mutant ( Arg 454 FAK ) , and a Src binding mutant ( Phe 397 FAK ) inhibited the accumulation of FAK at the bacterial entry site . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
For example , it provides a platform for protein tyrosine kinases such as FAK and SRC , which are activated as a result of adhesion or growth factor stimulation . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK was also associated with signaling molecules such as PLC gamma and PI 3 kinase through c Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This results from NEP induced inhibition of neuropeptide stimulated association of FAK with cSrc protein . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
They are regulated by many non receptor tyrosine kinases such as Src , Jak , Syk and FAK family kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The ability of FAK to mediate integrin signaling in the regulation of cell cycle progression depends on the phosphorylation of Tyr 397 , which implies a functional significance for the formation of FAK signaling complexes with Src , phosphatidylinositol 3 kinase ( PI3K ) and Grb 7 . ^^^ We have previously described a FAK mutant , D395A , that selectively disrupts FAK binding to PI3K , but allows FAK association with Src . ^^^ Using this mutation in a mislocalized FAK mutant background , we show here that formation of a FAK / PI3K complex is not sufficient for cell cycle progression but the formation of a FAK / Src complex plays an essential role . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , PTPepsilon stabilized binding of phosphorylated FAK to Src , suggesting this complex as a possible mediator of the PTPepsilon inhibitory response to insulin induced cell rounding and detachment in BHK IR cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here we report identification of PSGAP , a novel protein that interacts with PYK 2 and FAK and contains multiple domains including a pleckstrin homology domain , a rhoGTPase activating protein domain , and a Src homology 3 domain . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Additionally , FAK was linked to the hypertrophic response as follows : 1 ) coimmunoprecipitation of beta1D and FAK was detected ; 2 ) FAK overexpression induced ANF luciferase ; 3 ) rapid and sustained phosphorylation of FAK was induced by alpha ( 1 ) adrenergic stimulation ; and 4 ) blunting of the alpha ( 1 ) adrenergically modulated hypertrophic response was caused by FAK mutants , which alter Grb 2 or Src binding , as well as by FAK related nonkinase , a dominant interfering FAK mutant . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Integrin signals are relayed in part by focal adhesion kinase ( FAK ) activation and the formation of a transient signaling complex initiated by Src homology 2 ( SH 2 ) dependent binding of Src family protein tyrosine kinases to the FAK Tyr 397 autophosphorylation site . ^^^ Here we show that in viral Src ( 5 Src ) transformed NIH3T3 fibroblasts , an adhesion independent FAK Src signaling complex occurs . ^^^ Co expression studies in human 293T cells showed that 5 Src could associate with and phosphorylate a Phe 397 FAK mutant at Tyr 925 promoting Grb 2 binding to FAK in suspended cells . ^^^ In vitro , glutathione S transferase fusion proteins of the 5 Src SH 3 but not c Src SH 3 domain bound to FAK in lysates of NIH3T3 fibroblasts . ^^^ The 5 Src SH 3 binding sites were mapped to known proline 10 10 proline ( PXXP ) SH 3 binding motifs in the FAK N ( residues 371 377 ) and C terminal domains ( residues 712 718 and 871 882 ) by in vitro pull down assays , and these sites are composed of a PXXPXXPhi ( where Phi is a hydrophobic residue ) 5 Src SH 3 binding consensus . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , fibronectin mediated FAK phosphorylation at Tyr 397 was dramatically reduced in SYF cells ( deficient in Src , Yes , and Fyn expression ) . ^^^ Our results identify , for first time , the existence of Src dependent and Src independent pathways leading to FAK autophosphorylation at Tyr 397 stimulated by adhesion dependent signals and G protein coupled receptor agonists in the same cell . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
However , in PC 3 and DU 145 cells , FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine phosphorylation , tyrosine 861 , a Src specific site , is uncoupled from adhesion dependent signaling events . ^^^ Finally , inhibiting the FAK / Src signal transduction pathway by over expressing FRNK ( Focal adhesion kinase Related Non Kinase ) , an inhibitor of FAK activation , or treatment with PP 2 , a Src family kinase inhibitor , significantly inhibited migration of prostate carcinoma cell lines , demonstrating that tumor cell migration continues to be dependent on signals emanating from this pathway . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Differential regulation of cell migration and cell cycle progression by FAK complexes with Src , PI3K , Grb 7 and Grb 2 in focal contacts . ^^^
Interacting proteins: Q658W2 and 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Treatment of the cells with a Src family kinase inhibitor reduced the phosphorylation of Tyr 577 but not that of Tyr 397 , indicating that ezrin mediated FAK activation does not require the activity of Src kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Both null cells for pp 60 ( c src ) and triple knockout cells for pp 60 ( c src ) , pp 59 ( fyn ) , and pp 62 ( c yes ) exhibited decreased phosphotyrosine levels in focal contacts when compared with wild type cells . pp 60 ( c src ) null cells also exhibited faster assembly of cell matrix adhesions and a more exuberant recruitment of FAK to these sites . ^^^ Moreover , treatment of wild type cells with tyrphostin AG 1007 , which inhibits both pp 60 ( c src ) and FAK activity , induced accumulation of tensin in peripheral focal adhesions . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK autophosphorylation was sensitive to inhibitors of p160 / ROCK and coincided with the formation of stable complexes between FAK and Src family members . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This may be due to a competition between ACK 2 and FAK for Src , which is an essential cofactor for FAK activation , as we have found that ACK 2 specifically binds Src in cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Mechanical stimulation induces pp 125 ( FAK ) and pp 60 ( src ) activity in an in vivo model of trabecular bone formation . ^^^ Mechanical stimulation increased the association of FAK with Src and the time course of complex formation paralleled the temporal activation of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The functions and regulation of proteins associated with `` focal adhesion complexes ' ' ( membrane associated dense plaques ) in differentiated smooth muscle , including integrins , focal adhesion kinase ( FAK ) , c Src , paxillin , and the 27 kDa small heat shock protein ( HSP 27 ) are described . ^^^ Integrins in smooth muscles are key elements of mechanotransduction pathways that communicate with and are regulated by focal adhesion proteins that include FAK , c Src , and paxillin as well as proteins known to mediate cytoskeletal remodeling . ^^^ Evidence that functions of FAK and c Src protein kinases are closely intertwined is discussed as well as evidence that focal adhesion proteins mediate key signal transduction events that regulate actin remodeling and contraction . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The activity of c Src following fibronectin stimulation was decreased by about 30 % in Hic 5 expressing cells , and the effect of Hic 5 was restored by the overexpression of FAK and the constitutively active forms of Rho family GTPases , Rac 1 V12 and Cdc 42 V12 , but not RhoA V 14 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Autophosphorylation of FAK on Tyr 397 is generally a critical step for its activation , allowing the recruitment of Src family kinases , and phosphorylation of FAK and associated proteins . ^^^ PP 2 , an Src family kinase inhibitor , prevented the effects of cannabinoids on p 130 Cas and on FAK+6 , 7 tyrosines 577 and 925 , but not 397 , indicating that FAK autophosphorylation was upstream of Src family kinases in response to CB 1 R stimulation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
PP 2 , a Src family kinase inhibitor , or cytochalasin D , which selectively disrupts the network of actin filaments , inhibited both FAK phosphorylation and NO production induced by FN f , but the phosphatidylinositol 3 kinase inhibitor wortmannin had no effect . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Our results suggest that signals initiated by alphavbeta 3 promote metastasis in K 1735 melanoma cells through the phosphorylation of FAK and activation of Src . . ^^^
Interacting proteins: Q658W2 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 % . ^^^ Site specific FAK phosphotyrosine antibodies were used to determine that the carbachol stimulated increase in the autophosphorylation of FAK was unaffected by pretreatment with PP 1 , whereas the carbachol stimulated increase in the src family kinase mediated phosphotyrosine of FAK was completely blocked by pretreatment with PP 1 . ^^^ 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: Q658W2 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 . ^^^ Because residual FAK protein in ISIS 15421 treated A 549 cells was highly phosphorylated at the Tyr 397 / Src homology ( SH ) 2 binding site , expression of the FAK COOH terminal domain ( FRNK ) was also used as an inhibitor of FAK function . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src . ^^^ 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 . ^^^ However , FAK expression along with Src was found to be important for achieving high levels of CAS tyrosine phosphorylation in COS 7 cells , as well as recovery of CAS associated Src activity toward the SD . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , PDGF induced focal adhesion formation and activation of FAK , Src , and stress activated protein kinase 2 , p 38 , were dysregulated in the absence of EDG 1 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , phosphorylation of FAK , an Src adhesion substrate , is suppressed under these conditions . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Inhibition of Src with the specific inhibitor 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ( PP 2 ) completely blocked VEGF induced Y 861 phosphorylation without decreasing the level of phospho Y 397 FAK . ^^^ We also examined the role of Src in mediating endothelial functions of VEGF in which FAK has been implicated as having a role . ^^^ The Src inhibitor also decreased the anti apoptotic effect of VEGF determined by surface staining of annexin 5 but did not increase FAK proteolysis or prevent the VEGF dependent inhibition of FAK proteolysis . ^^^ These findings identify Src dependent FAK phosphorylation at Y 861 as a novel VEGF induced signalling pathway in endothelial cells and suggest that this pathway might be involved in the mechanisms mediating VEGF induced endothelial cell migration and anti apoptosis . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Expression of Src together with focal adhesion kinase ( FAK ) in suspended cells restores insulin induced receptor autophosphorylation to levels observed in fibronectin attached cells . ^^^ Conversely , expression of dominant negative mutants of either Src or FAK abolishes potentiation of insulin receptor phosphorylation by cell adhesion . ^^^ The results suggest that both Src and FAK participate in integrin mediated regulation of insulin receptor signal . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We found that three nonreceptor tyrosine kinases , focal adhesion kinase ( FAK ) , Src , and Etk / BMX play important parts in this process . ^^^ Etk / Bmx activation requires FAK and Src and is critical for neurotrophic factor induced growth , as LNCaP cells transfected with a dominant negative Etk / BMX fail to respond to bombesin . ^^^ Etk ' s activation requires FAK , Src , but not phosphatidylinositol 3 kinase . ^^^ Likewise , bombesin induced AR activation is inhibited by the dominant negative mutant of either Src or FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Immunoprecipitation of Fyn , a member of the Src family , from Abeta ( 25 35 ) treated neurons showed an increased association of Fyn with FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Using a wounded gastric epithelial cell monolayer model , we demonstrated that NSAIDs reduce both basal and epidermal growth factor ( EGF ) induced re epithelialization , and that this action involves disruption of actin stress fiber formation , reduced c Src activity , decreased phosphorylation of focal adhesion kinase ( FAK ) , tensin and their cellular re distribution . ^^^ Furthermore , NSAIDs significantly reduced EGF stimulated c Src association with FAK . ^^^ Nonsteroidal anti inflammatory drugs inhibit re epithelialization of wounded gastric monolayers by interfering with actin , Src , FAK , and tensin signaling . ^^^ Activation of Src and focal adhesion kinase ( FAK ) has been implicated in EGF stimulated cell migration . ^^^
Interacting proteins: Q658W2 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 . ^^^ Oncogenic Src promotes enhanced and deregulated FAK tyrosine phosphorylation which has been proposed to contribute to altered cell growth and / or morphological properties associated with transformation . ^^^ In this study , an inducible FAK expression system was used to study the potential role of FAK in 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 . ^^^ The FAK Tyr 397 autophosphorylation site was necessary for this scaffolding function , but was not required for 5 Src to stably interact with and phosphorylate FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Increases of diastolic pressure from approximately 0 to approximately 15 mmHg rapidly increased FAK tyrosine phosphorylation ( maximum : 2 . 3 fold ) and binding to c Src ( maximum : 2 . 8 fold ) and Grb 2 ( maximum : 3 . 6 fold ) . ^^^
Interacting proteins: Q658W2 and 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: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Concurrently , only TRAP disorganized the actin based cytoskeleton , with decrease in the cytoskeletal content of focal contact associated proteins like integrin alpha ( IIb ) beta ( 3 ) , Src , and focal adhesion kinase ( FAK ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Several src family kinases ( Fyn , Hck , Src ) are activated , as is the focal adhesion kinase p 125 FAK and , eventually , members of the p44 / p42 mitogen activated protein kinase ( MAPK ) family . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In viral Src ( 5 Src ) transformed cells , focal adhesion kinase ( FAK ) associates with 5 Src by combined 5 Src SH 2 and gain of function 5 Src SH 3 domain binding to FAK . ^^^ FAK signaling complex and FAK phosphorylation at Tyr 861 and Tyr 925 were reduced in 5 Src RT compared with 5 Src transformed cells . 5 Src but not 5 Src RT promoted Src / cell invasion through a reconstituted Matrigel basement membrane barrier and 5 Src co localized with FAK and beta ( 1 ) integrin at invadopodia . ^^^ Adenovirus mediated FAK overexpression promoted 5 Src RT recruitment to invadopodia , the formation of a 5 Src RT . ^^^ FAK signaling complex , and reversed the 5 Src RT invasion deficit . ^^^ Adenovirus mediated inhibition of FAK blocked 5 Src stimulated cell invasion . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Stretch induced tyrosine phosphorylation and activation of FAK and Src . ^^^ Stretch induced activation of p 38 MAPK was abolished by overexpression of FAT and CSK , which are inhibitors of the FAK and Src families , respectively , and was suppressed by overexpression of a dominant negative mutant of Ras . ^^^ These results suggest that mechanical stress activates p 38 MAPK and induces cardiac hypertrophy through the integrin FAK Src Ras pathway in cardiac myocytes . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Our goal was to determine the role of Src , focal adhesion kinase ( FAK ) , and platelet derived growth factor ( PDGF ) receptor signaling in the upstream initiation of these events . ^^^ Significant FAK Y ( 397 ) phosphorylation was observed only after 3 and 5 minutes of pressure stimulus and was blocked entirely by Src inhibition . ^^^ These data demonstrate that Src Y ( 418 ) autophosphorylation is an early event in pressure mechanotransduction and leads to activation of FAK Y ( 397 ) . ^^^ This finding suggests that Src may be the messenger that initiates and propagates the cellular growth response to pressure stimulus , and FAK is one of its downstream targets . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
There is evidence that integrin activation induces focal adhesion kinase ( FAK ) autophosphorylation at Y 397 and that Src binds to and is activated by FAK to carry out subsequent phosphorylation events . ^^^ In cells plated on fibronectin , FAK could indeed autophosphorylate at Y 397 independently of Src but with lower efficiency than when Src was present . ^^^ Src kinase activity was also required for phosphorylation of additional sites on FAK and for other integrin directed functions , including cell migration and spreading on fibronectin . ^^^ 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 . ^^^ Furthermore , our indirect evidence indicates that Src kinase activity does not need to be regulated to promote cell migration and FAK phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Moreover , formation of this FAK / alpha ( 5 ) beta 5 complex is significantly reduced in pp60c src deficient mice . ^^^ We find that VEGF stimulated Src activity in chick embryo blood vessels induces the coupling of focal adhesion kinase ( FAK ) to integrin alpha ( 5 ) beta 5 , a critical event in VEGF mediated signaling and biological responsiveness . ^^^ In cultured endothelial cells , VEGF , but not basic fibroblast growth factor , promotes the Src mediated phosphorylation of FAK on tyrosine 861 , which contributes to the formation of a FAK / alpha ( 5 ) beta 5 signaling complex . ^^^ Our findings indicate that Src can coordinate specific growth factor and extracellular matrix inputs by recruiting integrin alpha ( 5 ) beta 5 into a FAK containing signaling complex during growth factor mediated biological responses . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These cells overexpress urokinase receptor ( uPAR ) which , by activating alpha5beta1 integrin , initiates an intracellular signal through FAK and Src leading to ERK activation and tumorigenicity in vivo . ^^^ Down regulation of uPAR in these cells led to an approximately 3 5 fold reduction in FAK phosphorylation and association with Src and dormancy in vivo . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Further , since SuperFAK exhibited the same ability as wild type FAK to recruit Src family kinases , tyrosine phosphorylation of substrates was likely due to direct phosphorylation by FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Ang 2 ( 100 nM ) induced a rapid phosphorylation of Src ( peak approximately 2 min ) and focal adhesion kinase ( FAK , peak approximately 5 min ) followed by a decrease to basal levels in 30 min . ^^^ An increased association between FAK and Src in response to Ang 2 was detected after 1 min , which declined to basal levels after 30 min . ^^^ Treatment with the Src kinase inhibitor PP 1 inhibited FAK phosphorylation . ^^^ Furthermore , Src / FAK and Ca / CaM kinase activation serve as potential links between the Ang 2 receptor and MAPK activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
By employing the T338G Src mutant and [ gamma ( 32 ) P ] peATP analog , we demonstrate that c Src can directly phosphorylate focal adhesion kinase ( Fak ) in vitro . ^^^ We also show that incubation of permeabilized , T 338 Src expressing cells with peATP causes an increase in Fak tyrosine phosphorylation not observed in wild type Src cells . ^^^ Taken together , these data provide evidence that Src directly phosphorylates Fak and demonstrates the limitations of using this modified ATP strategy for analysis of direct substrates of protein kinases in permeabilized cells . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) and the related proline rich tyrosine kinase 2 ( PYK 2 ) are non receptor protein tyrosine kinases that transduce extracellular signals through the activation of Src family kinases and are highly enriched in neurones . ^^^ In intact nerve terminals , inhibition of Src kinases inhibited the membrane association of FAK , but not of PYK 2 , whereas tyrosine phosphatase inhibition sharply increased the membrane association of both FAK and PYK 2 . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of SSeCKS was apparent in cells deficient in Src , Fyn , Yes , or Abl tyrosine kinases or in NIH3T3 cells expressing a temperature sensitive 5 Src allele , but not in FAK deficient embryo fibroblasts . ^^^ Purified FAK or Src enzyme failed to directly phosphorylate SSeCKS in vitro . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These proteins include pCas ( 130 kDa ) , FAK ( 125 kDa ) , PI ( 3 ) k ( 85 kDa ) and src ( 85 kDa ) . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) and paxillin are known to form a complex with c Src at the focal contacts and to participate in the integrin mediated signal transduction as c Src substrates . ^^^ These findings collectively indicate that decidual c Src may activate signaling pathway ( s ) different from the integrin mediated signaling cascade involving FAK and paxillin . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , phosphorylation of the integrin regulated focal adhesion kinase ( FAK ) on Src specific sites is required for Src induced de regulation of E cadherin , demonstrating interdependence between integrin induced signals and cadherin associated adhesion changes induced by Src . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Transformation of cells by src like kinases leads to altered cell morphology associated with the disassembly of focal contacts and concomitant increase in tyrosine phosphorylation of pp 125 ( FAK ) 10 p 56 ( lck ) is a lymphocyte specific member of the src family of protein tyrosine kinases that associates with cell surface glycoproteins such as CD 4 and CD 8 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Modulation of either GT1b or GD 3 content affected phosphoinositol 3 kinase activation , and inhibition of this activation reversed the stimulation of cell spreading by anti GD 3 antibody , anti GT1b antibody , and ganglioside depletion , suggesting that phosphoinositol 3 kinase is an intermediate in both the FAK / Src and protein kinase C pathways that lead to cell spreading . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We then evaluated the association of FAK with c Src . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
The complex formation was further stimulated by c Src , in which JSAP 1 was tyrosine phosphorylated and other FAK / Src signaling molecules were recruited . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Calcitonin ( CT ) induced changes in Pyk 2 , FAK , and Erk1 / 2 phosphorylation were independent of c Src . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This FAK phosphorylation needs activation of the Src family tyrosine kinase ( s ) for which the 5 Crk SH 2 domain is responsible . 5 Crk was unable to activate the PI3K / AKT pathway in FAK null cells , indicating the functional importance of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We found that elastin receptor transduced signaling triggers activation of G proteins , opening of l type calcium channels , and a sequential activation of tyrosine kinases : FAK , c Src , platelet derived growth factor receptor kinase and then Ras Raf MEK1 / 2 ERK1 / 2 phosphorylation cascade . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This observation was further supported by the reduced complex formation between Src and 3F FAK ( 576F / 577F / 863F FAK ) as compared to that between Src and 576F / 577F FAK or Src and 863F FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Therefore , sustained activation of MAPK / ERKs through the Src / FAK pathway may contribute to the hyperproliferation observed in cystic kidneys from bcl 2 / mice . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Stimulation with LDL reveals ( 1 ) a major role for Tyr 925 phosphorylation which surpasses the phosphorylation of the other residues , including Tyr 397 , in rate and extent , ( 2 ) alphaIIbbeta 3 independent phosphorylation of Tyr 925 and Tyr 397 , and ( 3 ) complex formation between FAK and the Src kinase Fgr but not with c Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Autophosphorylation of FAK on Tyr 397 is a critical event , allowing binding of Src family kinases and activation of signal transduction pathways . ^^^
Interacting proteins: Q658W2 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: Q658W2 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 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Monosialyl Gb 5 organized with cSrc and FAK in GEM of human breast carcinoma MCF 7 cells defines their invasive properties . ^^^ Two human mammary carcinoma cell variants , MCF 7 / AZ and MCF 7 / 6 , show the same composition in their glycosphingolipid enriched microdomain ( GEM ) with regard to globo series structures Gb 3 , Gb 4 , Gb 5 , monosialyl Gb 5 , GM 2 , and cSrc and FAK . ^^^ Whereas invasiveness and motility of MCF 7 / AZ cells were enhanced greatly by treatment with mAb RM 1 directed to monosialyl Gb 5 , the same RM 1 treatment had no effect on MCF 7 / 6 . cSrc and FAK of MCF 7 / AZ , but not MCF 7 / 6 , were activated by RM 1 treatment . ^^^ Thus , malignancy of MCF 7 is highly dependent on monosialyl Gb 5 , and its activation of cSrc and FAK in GEM . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
CalA stimulated an increase in MLCP , Src kinase activity , an increase in the tyrosine phosphorylation of paxillin and focal adhesion ( FA ) kinase ( p 125 ( FAK ) ) , and monolayer hyperpermeability . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) was first identified as a viral Src ( 5 Src ) substrate , but the role of FAK in Src transformation events remains undefined . ^^^ We show that stable expression of the FAK C terminal domain ( termed FRNK ) in 5 Src transformed NIH 3T3 fibroblasts inhibited cell invasion through Matrigel and blocked experimental metastases in nude mice without effects on cell motility . ^^^ 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 . ^^^ Our findings show the importance of FAK in Src stimulated cell invasion and support a role for Src FAK signaling associated with elevated tumor cell metastases . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
IBE cells overexpressing wild type or R522K Shb ( with an inactive Src homology 2 ( SH 2 ) domain ) displayed increased FAK phosphorylation as well as enhanced spreading when seeded on collagen . ^^^ FGF 2 induced tyrosine phosphorylation of Shb was dependent upon Src activity but independent of FAK activation . ^^^ The data indicate that Shb binds directly to FAK and regulates its phosphorylation leading to enhanced cell spreading in a Src dependent manner . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , inhibiting Src tyrosine kinase decreases TNF induced focal adhesion kinase ( FAK ) tyrosine phosphorylation and cellular migration . ^^^ We therefore conclude that TNFR 2 activates a novel Src regulated pathway involving FAK tyrosine phosphorylation that enhances migration of intestinal epithelial cells . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Integrin mediated formation of src FAK and fyn FAK complexes was reduced or abolished in PTP alpha / cells on FN , concomitant with markedly reduced phosphorylation of FAK at Tyr 397 . ^^^
Interacting proteins: Q658W2 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 . ^^^ However , PI3K can not account for the Src independent pathway , since simultaneous inhibition of both PI3K and Src did not completely block effects of R Ras on FAK phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) is a non receptor tyrosine kinase that activates Src family kinases via SH 2 and SH 3 mediated interactions . ^^^ The data account for the different subcellular distribution of FAK and Src kinases and the specific regulation of the transduction pathways linked to FAK activation in the brain and implicate FAK in the regulation of membrane trafficking in nerve terminals . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here we show that viral Src ( 5 Src ) transformation of FAK / cells promotes integrin stimulated motility equal to stable FAK reexpression . ^^^ However , FAK / 5 Src cells were not invasive , and FAK reexpression , Tyr 397 phosphorylation , and FAK kinase activity were required for the generation of an invasive cell phenotype . ^^^ Cell invasion was linked to transient FAK accumulation at lamellipodia , formation of a FAK Src p130Cas Dock 180 signaling complex , elevated Rac and c Jun NH 2 terminal kinase activation , and increased matrix metalloproteinase expression and activity . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
During cell spreading , however , the activity of RhoA is reduced by a mechanism involving the tyrosine kinases c Src and focal adhesion kinase ( FAK ) , and the p190RhoGAP . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Besides coupling with heterotrimeric G proteins to activate phospholipase C beta ( PLC beta ) , AT1R also activates receptor tyrosine kinases ( PDGF R , EGF R and IGF R ) and non receptor tyrosine kinases ( Src , Fyn , Yes , proline rich tyrosine kinase 2 ( Pyk 2 ) , focal adhesion kinase ( FAK ) and JAK 2 ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Furthermore , p FAK Tyr ( 397 ) was shown to coimmunoprecipitate with beta 1 integrin , vinculin , and c Src both in vitro and in vivo using Sertoli germ cell cocultures and seminiferous tubules , respectively . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK signaling results from its ability to become highly phosphorylated in response to integrin mediated adhesion on Tyr 397 , permitting interactions with a number of different signaling effectors containing Src homology 2 ( SH 2 ) domains . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Inhibition of Src family kinases or caspases ( with PP 1 or benzyloxycarbonyl VAD fluoromethyl ketone , respectively ) delays FAK and AKT cleavage and cardiomyocyte detachment from substrate . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
It was found that hypoosmotic hepatocyte swelling led to an activation of Src ( but not FAK ) , Erks , and p38MAPK , which was prevented by the integrin inhibitory hexapeptide GRGDSP , but not its inactive analogue GRGESP . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
RESULTS : TUDC induced a rapid activation of focal adhesion kinase ( FAK ) and Src , as shown by an increase in Y 418 phosphorylation and a decrease in Y 529 phosphorylation of Src . ^^^ Inhibition of Src by PP 2 abolished the TUDC induced activation of p 38 ( MAPK ) but not of FAK and ERKs . ^^^ An integrin inhibitory peptide with an RGD motif blocked TUDC induced FAK , Src , ERK , and p 38 ( MAPK ) activation , suggesting that integrin signaling toward FAK / Src is required for TUDC induced MAPK activation . ^^^ CONCLUSIONS : TUDC induced stimulation of canalicular taurocholate excretion involves integrin sensing , FAK , and Src activation as upstream events for dual MAPK activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The expression of focal adhesion kinase ( FAK ) and Lyn , a Src family tyrosine kinase and substrate of FAK , was up regulated at both RNA and protein levels upon KAI1 / CD82 expression . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Using a panel of highly selective and structurally diverse Src inhibitors , we found that phosphorylation of signal transducer and activator of transcription 3 [ STAT 3 ( Y 705 ) ] and focal adhesion kinase [ FAK ( Y 861 ) ] was SFK dependent in cultured human colon , breast , lung , and ovarian tumor cells . ^^^ Additionally , treatment of mice with multiple Src inhibitors resulted in inhibition of phosphorylation of FAK ( Y 861 ) and of a putative Src autophosphorylation epitope ( Y 419 ) in HT 29 human colon tumor xenografts . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To elucidate the molecular mechanisms by which human epidermal growth factor receptor / heregulin ( HER2 / HRG ) influence the migratory potential of breast cancer cells , we have used phospho specific antibodies against c Src kinase and focal adhesion kinase ( FAK ) . ^^^ This study establishes that HER2 / HRG signaling selectively upregulates Tyr phosphorylation of c Src at Tyr 215 located within the SH 2 domain , increases c Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr 861 . ^^^ These findings suggest that HER2 / HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c Src tyrosine 215 . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) , a transducer of integrin , was only activated in 5 Src transformed cells . ^^^ Herbimycin A , an Src kinase inhibitor , reduced tyrosyl phosphorylation of FAK and reversed resistance to anoikis . ^^^ These data suggest that the ability of activated Src to prevent anoikis may be mediated by Src to a downstream signaling pathway involving FAK , but not Ras , PI 3 kinase , or PKC . . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
In contrast , adhesion dependent activation of FAK and c Src were not affected by CD 151 . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Recent evidence suggest that the tyrosine kinase c Src may mediate this proliferative response . c Src can signal through multiple intracellular signaling pathways including ( 1 ) the Shc / Grb2 / ERK2 pathway , ( 2 ) the signal transducers and activators of transcription ( STATs ) , ( 3 ) the focal adhesion kinase ( FAK ) signaling pathway , and ( 4 ) the phosphatidylinositol 3 kinase ( PI3K ) signaling pathway . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
CONCLUSIONS : These findings indicate that activation of Src tyrosine kinases Syk and PLCgamma 2 is not required for the initial stable attachment of human platelets to collagen and for FAK autophosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The rapid and efficient activation of MEK and phosphorylation on S 298 induced by cell adhesion to fibronectin is influenced by FAK and Src signaling and is paralleled by localization of phospho S 298 MEK1 and phospho MAPK staining in peripheral membrane proximal adhesion structures . ^^^ We propose that FAK / Src dependent , PAK 1 mediated phosphorylation of MEK 1 on S 298 is central to the organization and localization of active Raf MEK 1 MAPK signaling complexes , and that formation of such complexes contributes to the adhesion dependence of growth factor signaling to MAPK . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To better understand the pathways that regulate the choice between adhesion and cell death , we examined FAK , c Src andMAPKinase activities in SW 620 human colon cancer cells . ^^^ FAK , p 38 , c Src and ERK1 / 2 phosphorylation were assessed by Western blot in adherent cells and in cells prevented from adhesion by plating unto BSA pacificated dishes . p 38 and FAK were inhibited by SB 203580 ( 20 microM ) or by specific FAK antisense nucleotides or FAK siRNA , respectively , and adhesion quantitated . ^^^ RESULTS : Adhesion to collagen 1 nearly doubled FAK phosphorylation at Y 397 , the autophosphorylation site , and decreased p 38 activation by 60 % ( p < 0 . 001 ) but did not affect FAK phosphorylation at Y 576 , the c Src dependent site . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Since its initial discovery as a substrate and binding partner for the Src oncogene , a role for the focal adhesion kinase ( FAK ) in cancer has been speculated . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Accordingly , FAK phosphorylation and other downstream events , including MAPK phosphorylation , Src phosphorylation , focal adhesion formation , and cell spreading , are all significantly attenuated by inhibition of redox signaling . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Disrupting endogenous Fak / Src signaling either by expression of a dominant negative Fak mutant with phenylalanine substituted for Tyr 397 or by treatment with a c Src pharmacological inhibitor ( PP 2 ) markedly attenuated stretch induced Fak activation and clustering at myofilaments and inhibited stretch induced ANF gene activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
A novel role for FAK as a protease targeting adaptor protein : regulation by p 42 ERK and Src . ^^^ The nonreceptor tyrosine kinases Src and FAK regulate focal adhesion turnover by poorly understood mechanisms . ^^^ ERK / MAP kinase mediated activation of the protease Calpain 2 also promotes focal adhesion turnover ; however , it is not known if this is linked to the activities of Src and FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) and Src have been shown to be overexpressed in colon cancer . ^^^ Colon cancer cell lines overexpressed highly active Src and FAK . ^^^ Ad FAK CD induced apoptosis was significantly increased by PP 2 , an inhibitor of Src family kinases . ^^^ Activation of caspase 3 , down regulation of FAK , and Src and AKT activities were demonstrated in Ad FAK CD + PP 2 treated colon cancer cells undergoing apoptosis . ^^^ The results suggest that FAK and Src are both important survival factors , playing a role in protecting colon cancer cell lines from Ad FAK CD induced apoptosis . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The activation of c Raf by bFGF / alphavbeta3 not only depended on FAK , but also required p 21 activated kinase dependent phosphorylation of serine 338 on c Raf , whereas VEGF mediated c Raf phosphorylation / activation depended on Src , but not Pak . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The common model for integrin mediated signaling is based on integrin clustering and the potential for that clustering to recruit signaling molecules including FAK and src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Mechanistically , this appears to be due to reduced FAK and Src and elevated RhoA and Rock activities . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We initially observed that PRL dependent activation of focal adhesion kinase ( Fak ) , Erk1 / 2 , and cell proliferation was mediated by c Src in T47D cells , because expression of a dominant negative form of c Src ( SrcDM , K295A / Y527F ) blocked the PRL dependent effects . ^^^ However , in vitro , Fak and Jak 2 kinases were not directly inhibited by PP 1 , demonstrating the effect of PP 1 on c Src kinase as an upstream activator of Fak . ^^^ Moreover , we show that both c Src / PI3K and c Src / Fak / Erk1 / 2 pathways are involved in the up regulation of c myc and cyclin d 1 expression mediated by PRL . ^^^ The previous findings suggest the existence of two PRL dependent signaling cascades , initiated by the c Src mediated activation of Fak / Erk1 / 2 and PI3K pathways that , subsequently , control the expression of c Myc and cyclin D 1 and the proliferation of T47D and MCF 7 breast cancer cells . . ^^^ The Src inhibitor PP 1 abrogated PRL dependent in vivo activation of Fak , Erk1 / 2 , p70S6K , and Akt and the proliferation of T47D and MCF 7 cells ; Janus kinase 2 ( Jak 2 ) activation was not affected . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Compared with GEC on plastic substratum , adhesion to collagen increased activation of focal adhesion kinase ( FAK ) , c Src , and ERK and facilitated survival ( prevented apoptosis ) . ^^^ Glomeruli isolated from rats with PAN revealed increased beta 1 integrin expression , along with increased activation of FAK , c Src , and ERK , compared with controls . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The ability of the focal adhesion kinase ( FAK ) to integrate signals from extracellular matrix and growth factor receptors requires the integrity of Tyr 397 , a major autophosphorylation site that mediates the Src homology 2 dependent binding of Src family kinases . ^^^ However , the precise roles played by FAK in specific Src induced pathways , especially as they relate to oncogenic transformation , remain unclear . ^^^ Here , we investigate the role of FAK in 5 Src induced oncogenic transformation by transducing temperature sensitive 5 Src ( ts72v Src ) into p 53 null FAK+ / + or FAK / mouse embryo fibroblasts ( MEF ) . ^^^ At the permissive temperature ( PT ) , ts72v Src induced abundant tyrosine phosphorylation , morphological transformation and cytoskeletal rearrangement in FAK / MEF , including the restoration of cell polarity , typical focal adhesion complexes , and longitudinal F actin stress fibers . 5 Src rescued the haptotactic , linear directional , and invasive motility defects of FAK / cells to levels found in FAK+ / + or FAK+ / + [ ts72v Src ] cells , and , in the case of monolayer wound healing motility , there was an enhancement . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
We demonstrate here that US 28 signals through the non receptor protein tyrosine kinases Src and focal adhesion kinase ( FAK ) and that this activity is necessary for US 28 mediated SMC migration . ^^^ Src kinase complex , suggesting that US 28 activates Src before FAK . ^^^ FAK complex , which is sensitive to treatment with the Src inhibitor PP 2 , further highlighting the critical role of Src in US 28 activation of FAK . ^^^ These findings demonstrate that activation of FAK and Src plays a critical role in US 28 mediated signaling and SMC migration . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cotransfection studies demonstrated that SOCS 3 , and also SOCS 1 , interact with FAK in a FAK Y 397 dependent manner , and that both the Src homology 2 ( SH 2 ) and the kinase inhibitory region ( KIR ) domains of the SOCS proteins contribute to FAK binding . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
GnRH induction of cytoskeletal remodeling was correlated with significant increases in the tyrosine phosphorylation status of a series of cytoskeletal associated proteins , e . g . focal adhesion kinase ( FAK ) , c Src , and microtubule associated protein kinase ( MAPK or ERK1 / 2 ) . ^^^ In addition to the sensitivity of ERKs to cytoskeletal integrity , GnRH induced FAK and c Src kinase activation were sensitive to these agents and the fibronectin integrin antagonistic RGDS peptide . ^^^ Activation of ERK was dependent on its protein protein assembly with FAK and c Src at focal adhesion complexes . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Since these Shc isoforms have been implicated in the activation of protein kinase c Src , which is required for FAK tyrosine phosphorylation , the observed dephosphorylation of FAK and of the FAK substrate paxillin by OTA could be ascribed to the early down regulation of Shc isoforms . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Additionally , FAK Y925F expression blocked collagen 4 ERK activation . alpha ( 1 ) beta ( 1 ) Or alpha ( 2 ) beta ( 1 ) integrin blockade with alpha ( 1 ) or alpha ( 2 ) integrin subunit antibodies indicated that either integrin can mediate adhesion , cell spreading , and FAK , Src , and ERK activation on collagen 4 . ^^^ These results suggest a pathway for collagen 4 ERK activation requiring Src phosphorylation of FAK Y 925 not previously described for this matrix protein and suggest either alpha ( 1 ) beta ( 1 ) or alpha ( 2 ) beta ( 1 ) integrins can regulate Caco 2 spreading and ERK activation on collagen 4 via Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Stretch of beta 1 integrin activates an outwardly rectifying chloride current via FAK and Src in rabbit ventricular myocytes . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
PAF exposure induced binding of p 130 ( Cas ) , Src , SHC , and paxillin to FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant negative ; adenoviral FAK CD and decreased the apoptotic response in BT 474 and MCF 7 breast cancer cell lines . ^^^ We have also shown that expression of activated Src in breast cancer cells increased the expression of alpha 2 integrin and that overexpression of alpha 2 integrin suppressed FAK CD mediated loss of adhesion . ^^^ This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In this study , we observed that curcumin inhibited the kinase activity of 5 Src , which led to a decrease in tyrosyl substrate phosphorylation of Shc , cortactin , and FAK . ^^^ Remarkably , curcumin not only exerted its negative effect on FAK via the disappearance of Src mediated FAK phosphorylation , but also directly inhibited its enzymatic activity . ^^^ Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity was the abolishment of 5 Src mediated cell mobility . ^^^ To our knowledge , this is the first report indicating that curcumin can retard cellular growth and migration via downregulation of Src and FAK kinase activity . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Involvement of site specific FAK phosphorylation in sphingosine 1 phosphate and thrombin induced focal adhesion remodeling : role of Src and GIT . ^^^ Pharmacological inhibition of Src with Src specific inhibitor PP 2 abolished S1P induced translocation of FA proteins , cortical actin ring formation , and FAK [ Y 576 ] phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In this study , we further demonstrate that DcR 3 is able to induce actin reorganization and enhance the adhesion of monocytes and THP 1 cells by activating multiple signaling molecules , such as protein kinase C ( PKC ) , phosphatidylinositol 3 kinase ( PI3K ) , focal adhesion kinase ( FAK ) and Src kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We assessed binding affinity by detachment assay ; integrin surface expression by flow cytometry ; and focal adhesion kinase ( FAK ) , Src , and extracellular signal regulated kinase ( ERK ) activation by Western analysis and Src in vitro kinase assay . ^^^ We inhibited Src ( PP 2 ) , FAK ( small RNA interference , SiRNA , or FRNK transfection ) , MEK ( PD 98059 ) , PKC ( calphostin C ) , and actin destabilization ( phalloidin ) . ^^^ Pressure activated SW 620 FAK and Src , but not ERK . ^^^ Calcium inhibited adhesion but stimulated FAK ( but not Src ) . ^^^ PP 2 prevented pressure activation of Src , Src phosphorylation of FAK 576 , and pressure stimulated adhesion but not FAK 397 autophosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Disruption of Ca2+ dependent cell matrix adhesion enhances c Src kinase activity , but causes dissociation of the c Src / FAK complex and dephosphorylation of tyrosine 577 of FAK in carcinoma cells . ^^^ Activated c Src binds to FAK in the focal adhesion complex , resulting in the activation of the c Src / FAK signaling cascade , which regulates cytoskeletal functions . ^^^ However , the mechanisms by which c Src / FAK signaling is regulated during conditions of anchorage independent growth , a hallmark of tumor progression , are not clearly known . ^^^ Here , an in vivo approach to measure c Src activity was studied using phospho specific antibodies against phosphorylated Y 418 of c Src ( Src [ pY 418 ] ) , an autophosphorylation site of c Src , and phosphorylated Y 577 of FAK ( FAK [ pY 577 ] ) , a known substrate of c Src . ^^^ Using genetic and pharmacological approaches to modulate c Src activity , we showed that the levels of Src [ pY 418 ] and FAK [ pY 577 ] , and the formation of a c Src / FAK [ pY 577 ] complex correlated with the activation state of c Src in adherent cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
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: Q658W2 and P12931	Pubmed	SVM Score :0.0
THP 1 macrophages constitutively expressed activated FAK , ERK , and Src . ^^^ Exposure of macrophages to pressure decreased ERK and FAK Y 397 phosphorylation ( 77 . 6 + / 7 . 9 % , n = 7 , P < 0 . 05 ) but did not alter FAK Y 576 or Src phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Interleukin 8 confers androgen independent growth and migration of LNCaP : differential effects of tyrosine kinases Src and FAK . ^^^ Our evaluation of the possible signal pathways involved in androgen independence and cell migration shows that the tyrosine kinases Src and FAK ( focal adhesion kinase ) are involved in IL 8 induced signaling . ^^^ Pharmacological and genetic inhibitors of Src and FAK interfere with IL 8 induced cell migration , while only the Src inhibitor was able to repress androgen independent growth . ^^^ This suggests that both growth and migration depend on the activity of Src , whereas cell migration also requires the activation of FAK . ^^^ The observation that IL 8 mediates its growth and chemotactic effects via Src and FAK suggests the potential use for tyrosine kinase inhibitors at early stage of prostate cancer development . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here the role of integrins , Src , and focal adhesion kinase ( FAK ) in insulin signaling was investigated using the intact organ model of perfused rat liver . ^^^ Insulin increases [ Tyr ( P ) ( 418 ) ] Src , [ Tyr ( P ) ( 397 ) ] FAK , and dual p 38 ( MAPK ) phosphorylation by about 2 fold . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
MSU induced rapid tyrosine phosphorylation of Pyk 2 and FAK , their adaptor protein paxillin , and interacting kinase c Src . ^^^ MSU induced functional signaling by specific protein kinases ( p 38 , Src , and the focal adhesion kinase [ FAK ] family members proline rich tyrosine kinase 2 [ Pyk 2 ] and FAK ) was also examined using selective pharmacologic inhibitors and transfection of kinase mutants . ^^^ CONCLUSION : In chondrocytes , MSU crystals activate a signaling kinase cascade typically employed by adhesion receptors that involves upstream Src and FAK family activation and downstream p 38 activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although the Tyr kinases Src and FAK are known to activate ETK directly , Src is insensitive to AG 879 , and FAK is inhibited by 100 nM AG 879 , but not by 10 nM AG 879 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK Src signalling through paxillin , ERK and MLCK regulates adhesion disassembly . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK was critical for the subsequent phosphorylation of Src by gB Delta TM , and Src induction was essential for the phosphorylation of phosphatidylinositol 3 kinase ( PI 3K ) . ^^^ These findings suggest that , independently of other viral glycoproteins and via its RGD motif , HHV 8 gB induces integrin dependent pre existing FAK Src PI 3K Rho GTPase kinases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Stable platelet aggregation , adhesion , and spreading during hemostasis are promoted by outside in alphaIIbbeta 3 signals that feature rapid activation of c Src and Syk , delayed activation of FAK , and cytoskeletal reorganization . ^^^ In contrast , FAK interacts with alphaIIbbeta 3 and c Src , but not with Syk , in focal complexes and adhesions . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Dramatic alterations in the distribution of vinculin and in the expression and phosphorylation state of both FAK and Src kinases were also detected . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although HUVECs express the non receptor tyrosine kinases Fak , Src , and Etk which mediate neuropeptide signaling in CaP , they are not activated by neuropeptides in HUVECs . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These studies also shed light on the role of focal adhesion kinase ( FAK ) downstream of 5 Src and other signalling pathways in controlling migration , invasion and survival of transformed cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Consistently , activated kappa opioid receptor induced Src stimulation and FAK autophosphorylation and promoted the formation of Src FAK complex . ^^^ These studies demonstrate that the activation of JNK by kappa opioid receptors is routed via Gbetagamma , Src , FAK , Sos , Rac , and Cdc42 . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This revealed a Src dependent phosphorylation of a focal adhesion kinase ( FAK ) p 85 complex on glutamate stimulation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The association of Src family kinases with FAK and PYK 2 was also distinctively affected by ECS ; Src was mainly associated with PYK 2 while Yes was associated with FAK . ^^^ The phosphorylation of FAK and PYK 2 at the key tyrosine residue was not well correlated with the association with Src family kinases . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The expression of beta ( 1 ) integrin receptor , as well as Src , son of sevenless protein ( SOS ) and phosphorylated mitogen activated protein ( MAP ) kinases ( MAPK ) , extracellular signal regulated kinase 1 ( ERK ( 1 ) ) and kinase 2 ( ERK ( 2 ) ) but not focal adhesion kinase pp 125 ( FAK ) ( FAK ) , Shc , and Grb 2 was significantly decreased in cells incubated for 24 h with 10 microM AB ( 1 ) compared to the control , whereas in the same conditions chlorambucil did not evoke any changes in expression of all these signaling proteins , as shown by Western immunoblot analysis . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although NGF is known to bind to and activate the receptor tyrosine kinase TrkA , many downstream targets of NGF signaling may be possibly phosphorylated by nonreceptor tyrosine kinases such as c Src and focal adhesion kinase ( FAK ) . 2 . ^^^ Consistent with the possibility that NGF induces the proteolysis of FAK via recruitment of Src family kinases , the use of various phosphorylation site specific anti FAK antibodies revealed an NGF inducible and PP 1 sensitive accumulation of a putative fragment ( i . e . , p 62 ) of FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In TGF beta 1 induced apoptotic cells , c Src maintained its tight association with p 85 FAK fragment cleaved by caspases , possibly contributing to focal adhesion disassembly . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Further , a Src family kinases inhibitor , PP 2 , suppressed GRe and PHGPx mRNA by inactivation of FAK and c Src in HL 60 / FAK cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This mechanism was characterized by decreased recruitment of focal adhesion kinase ( FAK ) and vinculin to the alpha ( 5 ) beta 3 integrin and reduced FAK and Src activation in response to VEGF . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
CAS expression led to a substantial increase in the phosphotyrosine content of FAK and paxillin , supporting a role for CAS as a positive regulator of Src activity at integrin adhesion sites . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Hyperosmotic stress stimulated FAK phosphorylation at Tyr 397 occurred via a Src independent pathway , whereas Tyr 577 phosphorylation was completely blocked by exposure to the Src family kinase inhibitor PP 2 . ^^^ Our results indicate that FAK plays a fundamental role in protecting cells from hyperosmotic stress , and that the pathway ( s ) that mediates FAK autophosphorylation at Tyr 397 in response to osmotic stress can be distinguished from the pathways utilized by many other stimuli , including neuropeptides and bioactive lipids ( Rho and Rho associated kinase dependent ) , tyrosine kinase receptor agonists ( phosphatidylinositol 3 kinase dependent ) , and integrins ( Src dependent ) . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These results indicate that a major pathway for adhesion dependent activation of PI3K / Akt is triggered by the membrane proximal part of the beta 1 subunit in a FAK and Src independent manner . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Expression of phosphorylated ( P ) c Src , P focal adhesion kinase ( FAK ) , P Akt , P glycogen synthease kinase 3beta ( GSK 3beta ) , dephosphorylated ( DP ) beta catenin , and various integrins such as , alpha 3 , alpha 5 , beta 1 , beta 3 , and beta 4 was also increased in MMTV CR 1 tumors . ^^^ HC 11 / CR 1 cells treated with the c Src inhibitor PP 2 reduced the expression of P c Src and of P FAK , P Akt , P GSK 3beta , DP beta catenin all known to be activated by c Src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Direct stretch of beta 1 integrin activates an outwardly rectifying , tamoxifen sensitive Cl ( ) current ( Cl ( ) SAC ) via focal adhesion kinase ( FAK ) and / or Src . ^^^ Because myocyte stretch releases angiotensin 2 ( AngII ) , which binds AT 1 receptors ( AT1R ) and stimulates FAK and Src in an autocrine paracrine loop , we tested whether AT1R and their downstream signaling cascade participate in mechanotransduction . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Many cell responses signal through focal adhesion kinase ( FAK ) , often by integrin induced autophosphorylation of FAK or phosphorylation by Src family kinases . ^^^ Here , we used an interfering FAK mutant ( 4 9F FAK ) to show that Src dependent FAK phosphorylation is required for focal adhesion turnover and cell migration , by controlling assembly of a calpain 2 / FAK / Src / p42ERK complex , calpain activation , and proteolysis of FAK . ^^^ These data show that Src mediated phosphorylation of FAK acts as a pivotal regulator of both actin and adhesion dynamics and survival signaling , which , in turn , control apparently distinct processes such as cell migration and anchorage independent growth . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
CCh also induced association of FAK with the EGFr and FAK phosphorylation was attenuated by an EGFr inhibitor , tyrphostin AG 1478 , and an inhibitor of Src family kinases , PP 2 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
However , treatment of intact cells with the selective Src family kinase inhibitor PP 2 , at concentrations which abolished Src mediated phosphorylation of focal adhesion kinase ( FAK ) at Tyr 577 , unexpectedly led to increased phosphorylation at Src Tyr 418 and diminished phosphorylation at Tyr 529 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
PDGFR , not FAK or EGFR , appears to be the upstream protein tyrosine kinase responsible for the detachment induced Src activation in the lung tumor cells . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Here we show that netrin 1 induces tyrosine phosphorylation of proteins including focal adhesion kinase ( FAK ) and the Src family kinase Fyn . ^^^ Blockers of Src family kinases inhibited FAK phosphorylation and axon outgrowth and attraction by netrin . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Activation of FAK and Src are receptor proximal events required for netrin signaling . ^^^ Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase ( FAK ) . ^^^ Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC . ^^^ On the basis of our observations , we suggest a model in which DCC functions as a kinase coupled receptor , and FAK and Src act immediately downstream of DCC in netrin signaling . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Amplification and oscillations in the FAK / Src kinase system during integrin signaling . ^^^ In this paper , we focused on the molecular system formed by the two kinases FAK ( focal adhesion kinase ) and Src , which undergo auto and co activation during early steps of integrin signaling . ^^^ Furthermore , we show that when FAK activity is lower than Src activity , spontaneous oscillations of FAK phosphorylation forms may appear . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This was paralleled by increases of Fak / Src association and Src activity ( Tyr 418 phosphorylation ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This was accompanied by the loss of formation of a complex containing the IGF IR , RACK 1 , and beta 1 integrin ; loss of migratory capacity ; enhanced Src and FAK activity ; enhanced Akt phosphorylation ; and decreased p 38 mitogen activated protein kinase activity . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The Delta 375 truncation mutant of FAK is strongly phosphorylated both when Tyr 397 is mutated to phenylalanine , and in the presence of the Src inhibitor , PP 2 , suggesting that removal of the amino terminus can render FAK Src independent . ^^^ This is in contrast to the K38A mutant that is not phosphorylated in the Y397F background , and which shows decreased phosphorylation in the presence of the Src inhibitor PP 2 , suggesting that regulation of FAK by Src is a secondary step in its activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cell invasion and IL 8 production pathways initiated by YadA of Yersinia pseudotuberculosis require common signalling molecules ( FAK , c Src , Ras ) and distinct cell factors . ^^^ Tyrosine protein kinases , including the focal adhesion kinase ( FAK ) and c Src , as well as the small GTPase Ras , were shown to play a significant role in both YadA promoted cell processes . ^^^ Furthermore , IL 8 production and invasion induced by YadA were strongly reduced in FAK and c Src deficient cells and in cells overexpressing dominant interfering forms of FAK , c Src or Ras . ^^^ Moreover , inhibition of ERK1 / 2 by pharmacological agents or overexpression of dominant negative FAK , c Src or Ras abrogated IL 8 release , whereas invasion remained unaffected . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In conclusion , these results suggest that Ang 2 mediates an increase in FAK and paxillin phosphorylation and induces HUVEC migration through signal transduction pathways dependent on PI3K and Src tyrosine kinase activation and EGFR transactivation . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although integrin engagement initiates signaling events such as focal adhesion kinase ( FAK ) and Src kinase activation , the role of phosphoinositide turnover in cell adhesion is less clear . ^^^ Moreover , in cells null for Src family members , but not in cells null for FAK family members , integrin dependent PLC gamma 1 tyrosine phosphorylation was greatly reduced . ^^^ Finally , the data demonstrated that PLC gamma 1 co immunoprecipitated with Src following fibronectin induced integrin activation , and this association did not depend on FAK expression . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Src kinase activity is required for turnover of cell matrix adhesions and , in particular , the Src dependent phosphorylation of focal adhesion kinase ( FAK ) is required for their disassembly . ^^^ Surprisingly , we found that expression of SrcMF or Src 251 resulted in increased tyrosine phosphorylation of FAK on Tyr ( 407 ) , Tyr ( 576 ) , Tyr ( 577 ) , and Tyr ( 861 ) , which are considered to be Src kinase substrates . ^^^ This Src kinase independent phosphorylation of FAK required an intact Src SH 2 domain that mediates association of Src and FAK at peripheral adhesions . ^^^ Use of a novel highly potent and selective Src kinase inhibitor AP 23464 combined with experiments in Src / Fyn / Yes deficient fibroblasts showed that increased phosphorylation of FAK in cells expressing SrcMF did not require Src like kinases . ^^^ However , specific phosphorylation on Tyr ( 925 ) of FAK was not evident in SrcMF or Src 251 expressing cells , and lack of Src kinase dependent phosphorylation on this site was associated with impaired adhesion turnover . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Interestingly , the extent of both c Src dephosphorylation at Tyr 529 , FAK and paxillin phosphorylation , and the increased cell adhesion were associated with the degree of r PTPeta expression . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Prolidase activity and collagen biosynthesis are supposed to be regulated by beta ( 1 ) integrins , which initiate a signaling pathway in which several kinases and intracellular proteins are involved , including focal adhesion kinase pp 125 ( FAK ) ( FAK ) , Src , Shc , growth factor receptor bound protein 2 ( Grb 2 ) , son of sevenless protein ( SOS ) , Ras , Raf and mitogen activated protein kinases ( MAPK ) , extracellular signal regulated kinase 1 ( ERK ( 1 ) ) and kinase 2 ( ERK ( 2 ) ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Signal transduction molecules activated by these neuropeptides include Src , focal adhesion kinase ( FAK ) , ERK , and PI3K / Akt , with subsequent activation of Elk 1 , NF kappaB , and c myc transcription factors . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Total FAK phosphorylation was reduced in vessels at 150 mm Hg by treatment with the Src family kinase inhibitor PP 2 or with the integrin extracellular matrix interaction blocking RGD peptide , attaining 1 . 75+ / 0 . 22 fold and 2 . 00+ / 0 . 19 fold , respectively ( P < 0 . 05 ) , compared with 3 . 07+ / 0 . 38 fold ( P < 0 . 001 ) in untreated vessels . ^^^ CONCLUSIONS : Our results demonstrate that ( 1 ) steady and cyclic modes of stretch are transduced differently in the aorta , the former implicating FAK , the latter not , and ( 2 ) Src and integrins are involved in steady pressure induced FAK . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The CXCL12 / CXCR4 FAK pathway is membrane cholesterol dependent and impaired by metabolic inhibitors of G ( 1 ) , Src family , and the GTPase activating protein , regulator of G protein signaling 1 ( RGS 1 ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Transient forebrain ischemia effects interaction of Src , FAK , and PYK 2 with the NR2B subunit of N methyl D aspartate receptor in gerbil hippocampus . ^^^ Two different models of brain ischemia were used to examine the evoked changes in the tyrosine phosphorylation of NMDA receptor subunits 2A and 2B ( NR2A and NR2B ) , as well as their interactions with non receptor tyrosine kinases ( NRTKs : FAK , PYK 2 Src ) , and PSD 95 protein . ^^^ Concomitantly , an increased association of NR2B with FAK , PYK 2 , Src and PSD 95 has been observed . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
METHODS : We analyzed 162 node negative breast cancer cases to determine the prognostic relevance of FAK expression , and we investigated the relationship of FAK with major associated signaling pathways ( HER 2 , Src , Akt and extracellular regulated kinases ) by immunohistochemistry and western blot analysis . ^^^ Significant positive correlations were observed between elevated FAK expression and HER 2 overexpression ( P = 0 . 001 ) , as well as phospho Src Tyr 215 ( P = 0 . 021 ) and phospho Akt ( P < 0 . 001 ) , but not with phospho ERK1 / 2 ( P = 0 . 108 ) . ^^^ CONCLUSIONS : Immunohistochemical detection of FAK expression is of no prognostic significance in node negative breast cancer but provides evidence that HER 2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
IGF 1 increased tyrosine phosphorylation of the focal adhesion kinase ( FAK ) Pyk 2 ( calcium dependent proline rich tyrosine kinase 2 ) to a much greater extent than FAK , and increased association of Src with Pyk 2 but not FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Following autophosphorylation at tyrosine 397 , FAK binds the Src homology 2 domains of Src and phosphoinositide 3 kinase , among several other possible binding partners . ^^^ We hypothesize that the phosphorylated FAK peptide competes with the endogenous FAK for binding to FAK effectors including , but not limited to , Src and phosphoinositide 3 kinase , causing spatiotemporal misregulation and subsequent lamellar arrest . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Hyposmolarity also activated the non receptor tyrosine kinases , Src , focal adhesion kinase ( FAK ) , extracellular signal regulated protein kinase ( ERK ) 1 / 2 , and the tyrosine kinase target phosphatidyl inositol 3 kinase ( PI3K ) . ^^^ The hyposmotic induced activation of these kinases required the prior phosphorylation of ErbB 4 as shown by the effect of ErbB 4 blockade with AG 213 reducing by 85 95 % the phosphorylation of FAK and ERK1 / 2 , by 74 % and 36 % that of PI3K and Src , respectively . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Pathogen binding induced tyrosine phosphorylation of several host proteins associated with bacterial attachment sites , including FAK and the Src substrate cortactin . ^^^ In FAK deficient cells , local recruitment of cortactin still occurred , whereas the integrin and Src dependent tyrosine phosphorylation of cortactin was abolished . ^^^ As siRNA mediated gene silencing of cortactin or mutation of critical amino acid residues within cortactin interfered with uptake of S . aureus , our results reveal a novel functional connection between integrin engagement , FAK activation and Src mediated cortactin phosphorylation . ^^^ Cooperation between FAK , Src and cortactin in integrin mediated internalisation of bacteria also suggests a molecular scenario of how engagement of integrins could be coupled to membrane endocytosis . . ^^^
Interacting proteins: Q658W2 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 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These data suggest that ( 1 ) RPTPkappa positively regulates Src ; ( 2 ) HER 2 signaling and TGF beta induced RPTPkappa converge at Src , providing an adequate input for activation of FAK and increased cell motility and adhesion ; and ( 3 ) RPTPkappa is required for both the antiproliferative and the promigratory effects of TGF beta . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Increased extracellular pressure stimulates colon cancer cell adhesion by activating focal adhesion kinase ( FAK ) and Src . ^^^ We investigated the role of the cytoskeleton in pressure induced inside out FAK and Src phosphorylation and pressure stimulated adhesion . ^^^ We compared the effects of these agents on pressure induced SW 620 and human primary colon cancer cell adhesion and inside out FAK / Src activation with outside in adhesion dependent FAK / Src activation . ^^^ Phalloidin , cytochalasin D , latrunculin B and colchicine prevented pressure induced SW 620 FAK phosphorylation but not Src phosphorylation . ^^^ These results suggest that both cytoskeleton dependent FAK activation and cytoskeleton independent Src activation may be required for extracellular pressure to stimulate colon cancer cell adhesion . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These effects were explained in part by our observation in endothelial cells that Sema ECD inhibited VEGF mediated Src , FAK and ERK phosphorylation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
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 . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Cascades of activated proteins involve cytoplasmic membrane related proteins ( FAK complex , Src family tyrosine kinases ) , but also MAPK and NF kB pathways , leading to NO , prostanoid and cytokine production , and protease activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Src and FAK kinases cooperate to phosphorylate paxillin kinase linker , stimulate its focal adhesion localization , and regulate cell spreading and protrusiveness . ^^^ PKL is phosphorylated on tyrosine residues 286 / 392 / 592 by Src and / or FAK and these sites are required for PKL localization to focal adhesions and for paxillin binding . ^^^ The absence of either FAK or Src family kinases prevents PKL phosphorylation and suppresses localization of PKL but not GIT 1 to focal adhesions after Rac activation . ^^^ Expression of an activated FAK mutant in the absence of Src family kinases partially restores PKL localization , suggesting that Src activation of FAK is required for PKL phosphorylation and localization . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To further dissect the role of butyrate in anticarcinogenesis , its effect on cellular growth and invasion as well as the expression of c Src and FAK , two mutually interactive nonreceptor tyrosine kinases , in three different human colon cancer cell lines ( Caco 2 , SW 480 , and SW 620 ) were investigated . ^^^ In addition to growth inhibition , butyrate treatment results in a significant downregulation of c Src and FAK in human colon cancer cells , which can be attributable to their reduced transcripts and implicates the participation of a butyrate sensitive pathway in modulating their expression . ^^^ Concurrent to butyrate reduced c Src and FAK expression is the decrease of FAK Tyr decrease 397 phosphorylation . ^^^ Interestingly , in situ parallel enhancement of c Src and FAK was also observed in human colorectal tumor specimens . ^^^ These results imply that by virtue of suppression of c Src and FAK along with other butyrate targets in colonocytes , butyrate could effectively inhibit tumor growth and invasion . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The goal of this study was to examine the importance of the tyrosine kinases focal adhesion kinase ( FAK ) and Src kinase in cardiac ICl , swell regulation . ^^^ Pretreatment of the cells with the drug 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine , an inhibitor of FAK and Src , diminished swelling induced phosphorylation of these proteins but paradoxically increased ICl , swell . ^^^ Thus the tyrosine kinases FAK and Src contribute to the regulation of ICl , swell . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK mediated src phosphorylation of endophilin A 2 inhibits endocytosis of MT 1 MMP and promotes ECM degradation . ^^^ We found that 5 Src transformed cells activate a FAK dependent mechanism that attenuates endocytosis of MT 1 MMP . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Src and FAK signalling controls adhesion fate and the epithelial to mesenchymal transition . ^^^ Moreover , Src and the associated tyrosine kinase FAK are at the heart of the recently identified crosstalk between integrin and cadherin mediated adhesions of epithelial cells , particularly during the epithelial to mesenchymal transition . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Ablation of NMT 1 inhibited cell replication associated with a loss of activation of c Src and its target FAK as well as reduction of signaling through the c Raf / mitogen activated protein kinase / extracellular signal regulated kinase kinase / extracellular signal regulated kinase pathway . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Upon cell adhesion to extracellular matrix proteins , focal adhesion kinase ( FAK ) rapidly undergoes autophosphorylation on its Tyr 397 which consequently serves as a binding site for the Src homology 2 domains of the Src family protein kinases and several other intracellular signaling molecules . ^^^ In this study , we have attempted to examine the effect of the FAK Y397F mutant on 5 Src stimulated cell transformation by establishing an inducible expression of the Y397F mutant in 5 Src transformed FAK null ( FAK ( / ) ) mouse embryo fibroblasts . ^^^ We found that the FAK Y397F mutant had both positive and negative effects on 5 Src stimulated cell transformation ; it promoted 5 Src stimulated invasion , but on the other hand it inhibited the 5 Src stimulated anchorage independent cell growth in vitro and tumor formation in vivo . ^^^ However , the expression of the Y397F mutant rendered 5 Src transformed FAK ( / ) cells susceptible to anoikis , correlated with suppression on 5 Src stimulated activation of ERK and AKT . ^^^ 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 . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
We have previously shown that RET signals through focal adhesion kinase ( FAK ) in medullary thyroid cancer cells and that extracellular signal regulated kinase ( ERK ) activity can be blocked by pp 2 , an inhibitor of both Src and RET . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We examined the effect of adhesion signaling including Src and focal adhesion kinase ( FAK ) on cardiogenesis in mouse ES cells using alpha myosin heavy chain promoter driven enhanced green fluorescent protein or luciferase as reporters . ^^^ Surprisingly , although there was an interaction between Src and FAK in cardiogenesis , the procardiogenic effect of PP 2 appeared incompletely explained by Src kinase inhibition , since another Src family kinase inhibitor , SU 6656 , failed to induce cardiogenesis . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Following M CSF treatment , FAK and the active forms of M CSFR and Src were redistributed to the cytoskeleton , where active ERK , JNK and PI3K were detectable . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
FAK plays a central role in integrin signaling and Src activation . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
JSAP 1 mediated an association between FAK and JNK , which was induced by either co expression of Src or attachment of cells to FN . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
The effects on migration and invasion correlated with the inhibition of Src and downstream mediators of adhesion [ e . g . , focal adhesion kinase ( FAK ) , p 130 , and paxillin ] , and the cell cycle effects and apoptosis correlated with the induction of p 27 and the dephosphorylation of Rb . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
For alpha5beta1 , beta 1 mediated activation of focal adhesion kinase ( FAK ) promotes c Src recruitment to FAK and the formation of a FAK Src signaling complex . ^^^ Herein , we show that FAK expression is essential for alpha5beta1 stimulated cell motility and that exogenous expression of human alpha 4 in FAK null fibroblasts forms a functional alpha4beta1 receptor that promotes robust cell motility equal to the alpha5beta1 stimulation of wild type and FAK reconstituted fibroblasts . alpha4beta1 stimulated FAK null cell spreading and motility were dependent on the integrity of the alpha 4 cytoplasmic domain , independent of direct paxillin binding to alpha 4 , and were not affected by PRNK expression , a dominant negative inhibitor of Pyk 2 . alpha 4 cytoplasmic domain initiated signaling led to a approximately 4 fold activation of c Src which did not require paxillin binding to alpha 4 . ^^^ 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
A critical step in this process is the phosphorylation of Tyr 397 of FAK , which creates a binding site for Src family kinases , PI3K ( phosphoinositide 3 kinase ) and Shc ( Src homology and collagen homology ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
L 59 activated Src ( a known substrate of LAR ) , FAK and TrkB and also activated downstream signalling intermediates including PKC , ERK , AKT and CREB . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
AIM : To study the role of focal adhesion kinase ( FAK ) and its association with Src in hepatocyte growth factor ( HGF ) induced cell signaling in cholangiocarcinoma progression . ^^^ Western blotting , immunoprecipitation , and co immunoprecipitation were also performed to study the phosphorylation and interaction of FAK and Src . ^^^ A novel Src inhibitor ( AZM 555130 ) was applied in cultures to investigate the effects on FAK phosphorylation inhibition and on cell proliferation and invasion . ^^^ RESULTS : HGF enhanced HuCCA 1 cell proliferation and invasion by mediating FAK and Src phosphorylations . ^^^ FAK Src interaction occurred in a time dependent manner that Src was proved to be an upstream signaling molecule to FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In contrast , the inhibition of Src but not MAPK prevented ErbB FAK induced chemotaxis . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Phosphorylation at Tyr 397 activates FAK and creates a binding site for Src family kinases . ^^^ In addition , we found that phosphorylated alpha actinin bound to Src and reduced the binding of FAK to Src . ^^^ We propose that phosphorylated alpha actinin disrupts the FAK 10 Src complex exposing Tyr 397 in FAK to PTP 1B . ^^^ These findings uncover a novel feedback loop involving phosphorylated alpha actinin and PTP 1B that regulates FAK 10 Src interaction and cell migration . . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
In order to understand the molecular mechanism involved in these processes , we analyzed the phosphorylation of FAK and Src , two tyrosine kinases involved in migration and adhesion . ^^^ In Met F AEA treated cells , we observed a decreased tyrosine phosphorylation of both FAK and Src , this effect being attenuated by SR141716A . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Tyrosine phosphorylated CagA binds and activates SHP 2 phosphatase and the C terminal Src kinase ( Csk ) while inducing an elongated cell shape termed the `` hummingbird phenotype . ' ' Here we show that CagA reduces the level of focal adhesion kinase ( FAK ) tyrosine phosphorylation in gastric epithelial cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Moreover , a decrease in activated focal adhesion kinase ( FAK ) and Src kinase , key proteins involved in adhesion complex turnover , was observed when invasive breast cancer cells were treated with betaAPN . ^^^ Additionally , FAK and Src activation was increased in MCF 7 / LOX32 His cells , which was reversible on betaAPN treatment . ^^^ These results suggest that LOX facilitates migration and cell matrix adhesion formation in invasive breast cancer cells through a hydrogen peroxide mediated mechanism involving the FAK / Src signaling pathway . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The role of the tyrosine kinase Src in FAK ' s regulation will be discussed . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The non receptor tyrosine kinases c Src and focal adhesion kinase ( Fak ) mediate signal transduction pathways that regulate cell proliferation , survival , invasion , and metastasis . ^^^ Here , we investigated whether c Src and Fak are activated during progression of hormone dependent breast cancer . ^^^ Inhibition of c Src activity blocked proliferation of all tamoxifen resistant variants , suggesting that inhibitors of c Src Fak activity may delay or prevent progression and metastasis of ER positive tumors . ^^^ These studies also raise the possibility that fully active forms of c Src and Fak in breast tumors may be biomarkers to predict tamoxifen resistance and / or risk of recurrence in ER positive breast cancer . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Because FAK is a prominent substrate for the Src family of tyrosine kinases ( SFKs ) we tested for their involvement in the LHR mediated phosphorylation of FAK Tyr 576 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
This appears to occur through assembly of an EphB associated protein complex that includes focal adhesion kinase ( FAK ) , Src , Grb 2 , and paxillin and the subsequent activations of FAK , Src , paxillin , and RhoA . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Additionally , we have recently shown that LOX regulates cell migration , a key step in the invasion process , through a hydrogen peroxide dependent mechanism involving the focal adhesion kinase ( FAK ) / Src signaling complex . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In vascular smooth muscle cells ( VSMCs ) , through its G protein coupled AngII Type 1 receptor ( AT ( 1 ) ) , AngII activates various intracellular protein kinases , such as receptor or non receptor tyrosine kinases , which includes epidermal growth factor receptor ( EGFR ) , platelet derived growth factor receptor ( PDGFR ) , c Src , PYK 2 , FAK , JAK 2 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Protein tyrosine phosphatase alpha ( PTPalpha ) activates Src family kinases ( SFKs ) to promote the integrin stimulated early autophosphorylation of focal adhesion kinase ( FAK ) . ^^^ PTPalpha was dephosphorylated upon fibroblast detachment from the substratum and rephosphorylated when cells were plated on the integrin ligand fibronectin . alpha PTP phosphorylation occurred at Tyr 789 and required SFKs ( Src or Fyn / Yes ) , FAK , and an intact cytoskeleton . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The puncta co localized with focal adhesion kinase ( FAK ) and Src , and defined the distal tips of cell matrix adhesion sites identified with paxillin and vinculin . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Contribution of Src FAK signaling to the induction of connective tissue growth factor in renal fibroblasts . ^^^ Clustering of focal adhesion sites activated Src family kinases and focal adhesion kinase ( FAK ) . ^^^ On the other hand , when the fibroblasts were cultured on a rigid matrix , that is collagen coated plates , strong focal complexes prevented the dynamic alterations , and RhoA mediated upregulation of CTGF expression was independent of Src FAK signaling . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
MIT inhibited Src family kinases ( SFKs ) in cell free assays and led to the physical dissociation of FAK from the signaling complexes that it normally forms with c Src and Fyn in developing neurons . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To further characterize upstream signal transduction pathways that are required for HBx activity , including activation of Src and mitogen activated protein kinase ( MAPK ) cascades , we determined whether focal adhesion kinase ( FAK ) , a known regulator of Src family kinases and the other member of the Pyk2 / FAK kinase family , is activated by HBx . ^^^ Dominant inhibiting forms of FAK blocked HBx activation of Src kinases and downstream signal transduction , HBx stimulation of NF kappaB and AP 1 dependent transcription , and HBV DNA replication . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although the expression and / or activation status of focal adhesion complex components such as Src , FAK , and vinculin were not affected by Rac 1 deletion , the number and size of adhesion plaques were significantly reduced , and the molecular complex between Src , FAK , and vinculin was dissembled in Rac 1 null cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
To examine this , we engineered an R175L mutation in cSrc to prevent the interaction with FAK pY 397 . ^^^ Src binds to focal adhesion kinase ( FAK ) through its SH 2 domain and subsequently activates it for phosphorylation of downstream substrates . ^^^ Importantly , we were able to recapitulate wild type motile behavior and FA formation by directing the kinase to FAs , clearly implicating the SH 2 domain in recruitment to FAK and indicating that this targeting capacity , and not simply Src FAK scaffolding , was critical for normal Src function . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Altogether , these studies indicated a survival pathway mediated by the Src dependent activation of the PI 3 K / Akt pathway in a manner independent of FAK activity . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Neuregulin activates erbB 2 dependent src / FAK signaling and cytoskeletal remodeling in isolated adult rat cardiac myocytes . ^^^ We tested the hypothesis that erbB 2 signaling modulates focal adhesion formation via activation of a src / FAK pathway using adult rat ventricular myocytes in primary culture . ^^^ The erbB ligand neuregulin 1Beta ( NRG 1Beta ) induced phosphorylation of Src at Y 416 and Y 215 , and FAK at Y 861 . ^^^ Using antibody and pharmacological inhibitor strategies , we found that FAK activation was erbB 2 and Src dependent , but independent of PI 3 kinase / Akt pathway . ^^^ These results suggest the potential role of NRG 1Beta / erbB2 / Src / FAK signaling in the maintenance and repair of electrical and mechanical coupling in cardiomyocytes . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
The enhancement of cell motility and MMP 9 expression by CD 151 overexpression was abrogated by inhibitors and small interfering RNAs targeted to focal adhesion kinase ( FAK ) , Src , p 38 MAPK , and JNK , suggesting an essential role of these signaling components in CD 151 signaling pathways . ^^^ Meanwhile , CD 151 was found to be associated with alpha ( 3 ) beta ( 1 ) and alpha ( 6 ) beta ( 1 ) integrins in MelJuSo cells , and activation of associated integrins was a prerequisite for CD 151 stimulated MMP 9 expression and activation of FAK , Src , p 38 MAPK , JNK , and c Jun . ^^^ The homophilic interactions of CD 151 increased motility and MMP 9 expression of CD 151 transfected MelJuSo cells , along with FAK , Src , p 38 MAPK , and JNK mediated activation of c Jun in an adhesion dependent manner . ^^^ Furthermore , C 8161 melanoma cells with endogenous CD 151 were also shown to respond to homophilic CD 151 interactions for the induction of adhesion dependent activation of FAK , Src , and c Jun . ^^^ These results suggest that homophilic interactions of CD 151 stimulate integrin dependent signaling to c Jun through FAK Src MAPKs pathways in human melanoma cells , leading to enhanced cell motility and MMP 9 expression . . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Differential FAK phosphorylation occurred at the major autophosphorylation site Y ( 397 ) and Src phosphorylation site Y ( 861 ) . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Consistent with this observation , the levels of tyrosine phosphorylation of paxillin and pp125FAK were greatly reduced during mitosis , whereas the kinase activity of c Src was elevated . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In NIH / 3T3 cells transfected with the c src / F527 gene , an increase in the level of tyrosine phosphorylation of several proteins , including pp125FAK , within a group of proteins of 120 kDa , of p 85 ( cortactin ) , and of p 62 is observed , which is due to the elevated kinase activity of the resulting encoded pp60F527 protein . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Regulation of adhesion related protein tyrosine kinases during in vitro differentiation of retinal pigment epithelial cells : translocation of pp60c src to the nucleus is accompanied by downregulation of pp125FAK . ^^^ In the present report we show that induction of expression of a differentiated phenotype in cultured retinal pigmented epithelium of chick embryo is accompanied by coordinate regulation of expression and distribution of two adhesion related nonreceptor protein tyrosine kinases , pp60c src and pp125FAK . pp60c src translocates from the cell surface in flat undifferentiated cells to the nucleus in the packed differentiated cells . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
We describe distribution of these kinases in cells of retinal origin and show that two of them , pp125FAK and pp60c src redistribute intracellularly in a differentiation dependent manner . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Focal adhesion kinase ( FAK ) activation and tyrosine phosphorylation by Src were also delayed in KE 5 15 cells compared to parental cells . ^^^ Downregulation of Fes or FAK using small interfering RNA diminished Src activation by FGF 2 within FA . ^^^ These findings suggest that activation of Fes by FGF 2 enhances FAK dependent activation of Src within FA , promoting FGF 2 induced disassembly of focal adhesions . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Overexpression of FAK and its substrate c Src has been implicated in malignant transformation and acquisition of an invasive tumor phenotype of different tissues . ^^^ Overexpression of the multidomain protein paxillin , which is also a FAK ligand and a c Src substrate , has been associated with less malignant tumor behavior . ^^^ The purpose of this study was to analyze the involvement of integrin signaling molecules FAK , c Src , and paxillin in malignant transformation of the breast epithelium . ^^^ Using phosphospecific antibodies FAK pY ( 397 ) and Src pY ( 416 ) , we demonstrated that neither activation of FAK nor activation of c Src correlates with development of invasive tumor properties . ^^^ However , activation of both FAK and c Src correlates with malignant transformation . ^^^
Interacting proteins: Q658W2 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: Q658W2 and P12931	Pubmed	SVM Score :0.0
Immunofluorescence microscopy revealed that multiple signaling molecules ( e . g . , pp60c src , pp125FAK , phosphatidylinositol 3 kinase , phospholipase C gamma , and Na+ / H+ antiporter ) involved in both integrin and growth factor receptor signaling pathways became associated with the CSK framework of the FAC within 15 min after binding to beads coated with integrin ligands . ^^^ Western blot analysis confirmed that FACs isolated using RGD beads were enriched for pp60c src , pp125FAK , phospholipase C gamma , and the Na+ / H+ antiporter when compared with intact CSK or basal cell surface preparations that retained lipid bilayer . ^^^ Most importantly , isolated FACs continued to exhibit multiple chemical signaling activities in vitro , including protein tyrosine kinase activities ( pp60c src and pp125FAK ) as well as the ability to undergo multiple sequential steps in the inositol lipid synthesis cascade . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine phosphorylated proteins , including pp125FAK and paxillin , a majority of protein which bound to Csk was IRS 1 when cells were stimulated by insulin . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Tyrosine phosphorylation and activation of pp60c src and pp125FAK in bradykinin stimulated fibroblasts . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Since tyrosine phosphorylation of cytoskeleton associated proteins pp125FAK and cortactin were abolished in EGF stimulated SrcK cells , we concluded that , in contrast to Ras , Src kinases may control epithelial cell dispersion in the absence of gene expression and by directly regulating the organization of the cortical cytoskeleton . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Recent studies have shown that Src , through its SH 2 domain , stably associates with pp125FAK and that this association prevents dephosphorylation of pp125FAK in vitro by protein tyrosine phosphatases . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
At least two classes of protein tyrosine kinases are activated during various stages of platelet activation , 1 ) Src family tyrosine kinases are activated during an early phase of platelet activation by an integrin independent mechanism and 2 ) pp125FAK is activated during a late stage of platelet activation , and it is dependent on platelet aggregation mediated by fibrinogen binding to alpha IIb beta 3 . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
In particular , the 5 Src oncoprotein resides in cellular focal adhesions , where it induces tyrosine phosphorylation of pp125FAK and focal adhesion loss during transformation . 5 Src is translocated to cellular focal adhesions by an actin dependent process . ^^^ Moreover , switching the constitutively kinase inactive or myristylation defective temperature sensitive 5 Src proteins to the permissive temperature resulted in concomitant association with tyrosine phosphorylated focal adhesion kinase ( pp125FAK ) and redistribution of both to focal adhesions . ^^^ However , both catalytic activity and myristylation mediated membrane association are required to induce dissociation of pp125FAK from 5 Src , later degradation of pp125FAK and focal adhesion turnover during transformation and cell motility . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Finally the tyrosine kinase src , which could phosphorylate pp125FAK , was found to be activated in a [ Ca2+ ] 1 dependent way during stretch . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Moreover , immunoprecipitation of pp60c src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c src and tyrosine phosphorylated pp125FAK . ^^^ Our data suggest that de novo expression of the alpha5beta1 integrin in HT 29 colon cancer cells restores signaling via pp125FAK and pp60c src . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
Using immunoprecipitation assays coupled to Western blot analysis , we demonstrate here the collagen dependent association of paxillin and Src with pp125FAK . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
No change in pp125fak tyrosine phosphorylation nor in Src activity was detected . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
It resulted from decreased activity of Src family tyrosine kinase and / or decreased amount of Src kinase interacting with pp125FAK . ^^^ Furthermore , phosphorylation of Tyr 861 was reduced substantially by the Src family kinase inhibitor , PP 1 , while overexpression of Src kinase increased its phosphorylation , implying that Src kinase regulates phosphorylation of pp125FAK at Tyr 861 . ^^^ All of these findings suggest that increased phosphorylation of pp125FAK at Tyr 861 correlates with Ras induced transformation of fibroblasts , and TSA is able to detransform them through regulation of pp125FAK phosphorylation at Tyr 861 by an Src family kinase . . ^^^
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q658W2 and P12931	Pubmed	SVM Score :0.0
NA