| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :1.5186675 |
| Studies with Rat . 2 fibroblasts overexpressing activated Neu revealed that c Src requires the presence of tyrosine phosphorylated Neu for its ability to interact with Neu in vivo . 1.5186675^^^ Although both c Src and c Yes kinase associate with Neu in vivo , a tyrosine phosphorylated protein of 89 kd ( p 89 ) was found associated with c Src but not with c Yes in cell lysates derived from mammary epithelial cells transformed by either Neu or PyV middle T antigen . 0.53512384^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :1.9922169 |
| Here , we demonstrate that c Src requires tyrosine phosphorylated Neu for its ability to associate with Neu in vivo and this association is likely the result of a direct physical binding of c Src SH 2 domain to the tyrosine phosphorylated Neu . 1.9922169^^^ Taken together , these observations suggest that activation of c Src by these two closely related EGFR family members results from a direct and specific interaction of c Src with tyrosine phosphorylated Neu . . 0.9359376^^^ Moreover , in established cell lines expressing elevated levels of EGFR , EGF stimulation results in transphosphorylation of Neu and formation of complexes between c Src and tyrosine phosphorylated Neu . 0.57580891^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.96006335 |
| Moreover , activation of c Src was correlated with its ability to complex tyrosine phosphorylated Neu both in vitro and in vivo . 0.96006335^^^ Together , these observations suggest that activation of the c Src tyrosine kinase during mammary tumorigenesis may occur through a direct interaction with activated Neu . . 0.78002141^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The mucosal samples were snap frozen and subsequently stained with monoclonal antibodies to the following oncogene associated proteins ; c erbB 2 ( neu and CE 1 ) ( external domain ) , c erbB 2 ( NCL CB 11 ) ( internal domain ) , c src , c ras , c myc , c fos , c jun , and the onco suppressor gene p 53 . ^^^ In Barrett ' s epithelium , nine specimens were positive for c erbB 2 ( neu and CB 11 ) , three were positive for c src , two were positive for c ras and c jun , and one was positive for c fos . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The expression of mRNA of EGF receptor gene and ERBB 2 by TMK 1 cells was not changed by erbstatin treatment , whereas that of c src was slightly decreased . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The development of these mammary tumors was correlated with the tyrosine phosphorylation of Neu and the recruitment of c Src to the Neu complex . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Activation of erbB 2 and c src in phorbol ester treated mouse epidermis : possible role in mouse skin tumor promotion . ^^^ Concomittantly , erbB 2 : EGFr heterodimer formation and c src kinase activity were also elevated in TPA treated epidermis . ^^^ Activation of erbB 2 and c src kinase were also observed in the epidermis of TGF alpha transgenic mice where expression of human TGF alpha was targeted to basal keratinocytes with the human K 14 promoter . ^^^ In addition , activation of c src may be an important downstream effector in mouse keratinocytes both in vivo and in vitro , following activation of the EGFr , erbB 2 , or both . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| C Src activation by ErbB 2 leads to attachment independent growth of human breast epithelial cells . ^^^ Transformation with ErbB 2 , but not ras , resulted in a 5 6 fold increase in c src activity without affecting c src content of cells . ^^^ Similar activation of c src by ErbB 2 was also observed in other non tumorigenic mammary epithelial cells , including the human line MCF10A and the mouse line NMuMG . ^^^ Activation of c src appeared to be dependent on active ErbB 2 tyrosine kinase , as the ErbB 2 inhibitor tyrphostin AG 825 blocked the induction of c src kinase activity , as well as the ability of transformed cells to grow on soft agar , but not plastic . ^^^ The src selective inhibitor PP 1 effectively reduced c src activity , as well as growth of ErbB 2 transformed cells on soft agar , but not on plastic . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| In this study we show that the induced expression of c SRC antisense RNA or the application of a selective Src kinase inhibitor induces growth arrest , programmed cell death and reverses the transformed properties of cells that overexpress EGFR or HER 2 receptors . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin and HER 2 signaling selectively activates c Src phosphorylation at tyrosine 215 . ^^^ HER 2 overexpressing tumors showed increased levels of c Src phosphorylation at Tyr 215 . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Biochemical studies revealed that TKI 28 potently inhibited the activities of tyrosine kinases such as ErbB 2 , EGFR , KDR , PDGFRbeta , c kit and c Src , but had little effect on Flt 1 in cell free system . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The c Src tyrosine kinase associates with the catalytic domain of ErbB 2 : implications for ErbB 2 mediated signaling and transformation . c Src associates with and is activated by the ErbB 2 receptor tyrosine kinase , but is unable to bind the EGFR . ^^^ Although c Src has been found to interact directly and specifically with the ErbB 2 receptor , the significance of this interaction is unclear . ^^^ Using both chimeric receptor and site directed mutagenesis approaches , the region of interaction of c Src on ErbB 2 was identified . ^^^ Significantly , EGFR could be converted into a receptor capable of binding c Src by replacement of a catalytic domain of ErbB 2 . ^^^ ErbB 2 dependent activation of c Src results in disruption of epithelial cell cell contacts leading to cell dispersal that correlates with the re localization of phospho MAPK to focal adhesions . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Mammary epithelial cells isolated from tumors of double transgenic mice display increased tyrosine phosphorylation , c Src , and Akt activation compared with cells derived from HER 2 Neu tumors . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| A Tyr Phe substitution of erbB 2 Tyr 877 homologous to pp60c src Tyr 416 did not alter erbB 2 biological and biochemical properties , thus excluding the possibility that phosphorylation of this residue , located in the kinase domain , modulates erbB 2 gp 185 catalytic function . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Co expression studies in insect cells have shown that p 85 alpha and p 85 beta are substrates for the protein tyrosine kinases of epidermal growth factor , colony stimulating factor 1 and c erbB 2 receptors and the src family kinase p59c fyn . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| A detailed analysis of the NIH 3T3 transformants generated from REC : myc : gamma 33 and gamma 41 DNA failed to detect Ha ras , Ki ras , raf , neu , trk , abl , fms , or src oncogenes of rat origin . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| As demonstrated for transformed human fibroblasts , the morphology of neu , ras , src and sis transformed mouse fibroblasts became more normal after glucocorticoid treatment . ^^^ Moreover , treatment of the neu , ras , src and sis transformed cells with glucocorticoids resulted in a change in morphology but no increase in cell surface fibronectin . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The hypothesis is supported by the fact that many cancer cells have some dysfunction in gap junctional intercellular communication , many tumor promoting chemicals and several oncogenes ( i . e . , ras , src , mos , neu , but not myc ) reduce gap junctional intercellular communication , and several growth factors ( i . e . , EGF , TGF beta , bovine pituitary extract ) inhibit gap junction function . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Probes utilized represent 11 known oncogenes ( erbB 1 , gli , neu , myc , L myc , N myc , H ras , K ras , N ras , sis , and src ) . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| In addition to ras , the mos , fos , src , and erbB 2 oncogenes transformed this mutant with the same temperature dependence as described above ; polyomavirus middle T antigen , adenovirus type 12 , and human papillomavirus 16 E 67 also transformed , but without temperature dependence . ^^^ These results suggest that ras , fos , mos , src , and erbB 2 use a common cellular pathway for transforming cells . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Analysis of cellular oncogenes showed that myc and fps were amplified approximately tenfold and threefold , respectively , in this cell line , whereas N myc , L myc , N ras , K ras , H ras , abl , erbB 2 , Blym , src , raf 1 , myb , and sis were not changed significantly . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Comparison of the exon structure of the tyrosine kinase domain of the INSR with the corresponding regions of the human SRC , ROS , and ERBB 2 ( NGL ) protooncogenes indicates that the exon intron organization of this region has not been well conserved . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Transcripts coding for transcription factors ( RB , P 53 , FOS , MYC , MYB , ERBA , REL ) , growth factors ( FGF 1 , FGF 2 , INT 2 , TGFA , TGFB , PDGF , IGF 1 , IGF 2 ) , interleukins , ( IL 1 , IL 2 , IL 3 , IL 4 , IL 6 , TNF ) , growth factor receptors or cytosolic protein kinases ( RAF , PIM , FES , MET , SRC , ROS , TRK , KIT , CSFR , IGFR , PDGFR , EGFR , NEU ) were quantified in cultured human mammary fibroblasts from normal tissues , benign tumours , carcinomas and post radiation fibrosis lesions by slot blot autoradiography and image analysis . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Evidence is also presented that suggests that an EGF R related protein , ErbB 2 , may be involved in similar Src mediated interactions . ^^^ Overexpression of Src , EGF R , and / or ErbB 2 in breast and colorectal tumor cells suggests the potential that such interactions may contribute to the transformed phenotype of these carcinomas . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki ras , N ras , raf , trk , abl , fms , src , mos , fos , sis , fps , erbA , erbB or neu oncogenes of REC origin , and none were detected . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| DNA probes for the NRAS , HRAS , KRAS 2 , LCK , RAF 1 , MET , MYCL 1 , MYCN , MYB , ERBB 2 , FOS , CSF1R , and SRC protooncogene loci ; the retinoblastoma gene locus ( RB 1 ) ; the tumor virus integration sites INT 2 , PVT 1 , and MLV 12 ; and the locus of the tumor specific antigen T1A were used to screen mouse genomic DNAs from RF / J , CAST / Ei , MOLF / Ei , Mus musculus musculus , M . m . poschiavinus , and M . spretus . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Moreover , the exchange activity is constitutively enhanced in NIH 3T3 cells transformed by Src and ErbB 2 oncogenic tyrosine protein kinases ( TPKs ) , whereas transformation by oncogenic Mos and Raf does not alter the activity . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Expression of various oncogenes ( ras , myc , erbB 2 , src , fyn , yes and sis ) in a high metastatic clone ( MH 02 ) derived from a murine methylcholanthrene induced fibrosarcoma A ( Meth A ) was compared with those of its parent clone ( ML 01 ) by Northern blot analysis . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Both sup+ and sup clones could be transformed to anchorage independence by ras , src , mos , neu , polyoma mT and SV 40 suggesting that neither the presence nor the absence of the suppressor gene in BHK limits the transforming ability of these common oncogenes . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The morphology and GJIC of rat liver epithelial cells transformed with other oncogenes ( src , neu , and raf / myc ) were not affected by lovastatin . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| We also evaluated these inhibitor ' s effects on proteins that regulate ras function , which is a convergence point for signaling through both src family kinases and a number of growth factor receptors with tyrosine kinase activity ( e . g . , epidermal growth factor and erbB 2 receptors ) . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Elevated PDGFalphaR gene expression during serum starvation was not observed in cells that had been transformed with oncogenes erbB 2 , src , or raf , which prevent starvation induced growth arrest . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Immunoblotting identified two peripheral membrane tyrosine kinases , p6O ( src ) and p 120 ( abl ) , stably associated with the p 185 ( neu ) containing signal transduction particle . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Compared with normal rat liver epithelial cells , cells neoplastically transformed by src , neu , ras , and myc / ras all displayed reduced degrees of GJIC , reduced levels of membrane associated Cx 43 plaques , and hypophosphorylation of Cx 43 . ^^^ Confocal analysis further demonstrated that the Cx 43 protein was localized , at least in part , to the nucleus rather than to the plasma membrane in the src and neu transformed cells , but not in the ras and myc / ras transformed cells . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| While isoproterenol treatment increased steady state mRNA levels for fos , jun , myc , src , c erbB 2 , ras and topo 2 , inclusion of pefloxacin with the isoproterenol regimen blocked these increases . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Structural determinants of the interaction between the erbB 2 receptor and the Src homology 2 domain of Grb 7 . ^^^ The Src homology 2 ( SH 2 ) domain containing protein Grb 7 and the erbB 2 receptor tyrosine kinase are overexpressed in a subset of human breast cancers . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Substantial evidence exists supporting direct roles for ErbB 2 / neu and Src kinase activation in breast cancer . ^^^ Moreover , CHK was able to down regulate ErbB 2 / neu activated Src kinases . ^^^ These studies indicate that CHK binds , via its SH 2 domain , to Tyr 1253 of the activated ErbB 2 / neu and down regulates the ErbB 2 / neu mediated activation of Src kinases , thereby inhibiting breast cancer cell growth . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The receptor ( R ) for epidermal growth factor ( EGF ) is expressed at high levels on human breast cancer cells and associates with ErbB 2 , ErbB 3 , and Src proto oncogene family protein tyrosine kinases ( PTKs ) to form membrane associated PTK complexes with pivotal signaling functions . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our results indicate that dramatic reduction of caveolin 1 expression occurs in mammary tumors derived from c Neu expressing transgenic mice and other transgenic mice expressing downstream effectors of Neu mediated signal transduction , such as Src and Ras . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 binding to peptides containing the Src homology 2 domain of Grb 2 or p 85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , we provide evidence that EGF and neu differentiation factor induced Stat activation are dependent on Src but not Jak kinases . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our results showed that even though cellular transformation by src and neu has similar consequences , such as focal adhesion disassembly and increased metastasis potential , the molecular events underlying the signaling pathways can be dramatically different . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Tumor suppressor genes ( p 53 , p 16 ) , oncogenes ( c erbB 2 , H ras , K ras , cyclin D 1 , src ) , and growth factor / receptor ( TGF alpha , EGFR ) seem to cause the malignant transformation of Barrett ' s esophagus . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Src and Fyn are associated with acetylcholine receptors ( AChRs ) in muscle cells , and Src and Yes can act downstream of ErbB 2 , suggesting roles for Src family kinases in signaling pathways regulating neuromuscular synapse formation . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| AP 1510 treatment induced tyrosine phosphorylation of ErbB 1 and ErbB 2 homodimers and recruitment of Src homology 2 domain containing proteins ( Shc and Grb 2 ) . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Many tyrosine kinases , such as the epidermal growth factor receptor , Her 2 / Neu , Src , and Axl , are known to play a role in oncogenic signals in transformed cells . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The neu induced growth and invasive phenotypes could be reversed by drugs that inhibit Ras and Src activity . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Analyses of the members of the HRG stimulated complex revealed that RAFTK is associated with p 190 RhoGAP ( p 190 ) , RasGAP and ErbB 2 , and plays an essential role in mediating the tyrosine phosphorylation of p 190 by Src . ^^^ In addition , upon HRG stimulation of T47D cells , association of ErbB 2 with RAFTK was observed and found to be indirect and mediated by Src . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cyclin D 1 protein levels are elevated by mitogenic and oncogenic signaling pathways , and antisense mRNA to cyclin D 1 inhibits transformation by the ras , neu , and src oncogenes , thus linking cyclin D 1 regulation to cellular transformation . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The GnT 2 promoter , unlike the GnT 5 promoter , is not activated by either src or neu . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cyclin D 1 is overexpressed in 20 30 % of human breast tumors and is induced both by oncogenes including those for Ras , Neu , and Src , and by the beta catenin / lymphoid enhancer factor ( LEF ) / T cell factor ( TCF ) pathway . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Overexpression of gene 33 protein in mouse fibroblasts inhibited ( 1 ) cell proliferation driven by ErbB 2 but not by serum , ( 2 ) cell transformation induced by ErbB 2 but not by Ras or Src , and ( 3 ) sustained activation of ERK 1 and 2 by ErbB 2 but not by serum . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| For this purpose , we used PP 1 , an inhibitor specific for Src family kinases , which does not inhibit either EGF receptor or ErbB 2 . ^^^ CONCLUSION : Like EGF receptor and ErbB 2 , a member of Src family kinases ( most likely a new Src related kinase called `` Ray ' ' ) is essential for the Ras induced activation of PAK and the malignant transformation both in vitro and in vivo . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Activated oncogenes ( e . g . , ras , src , HER 2 ) induce co expression of angiogenic properties concomitantly with several highly selectable traits ( increased mitogenesis , resistance to apoptosis ) , a circumstance that may accelerate selection of the angiogenic phenotype at the cell population level . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Src family kinases and HER 2 interactions in human breast cancer cell growth and survival . ^^^ Seventy five per cent of the tumor tissues overexpressed HER 2 , while 64 % overexpressed c Src . ^^^ This result suggests that HRG may act through both HER 2 and c Src to facilitate anchorage independent growth . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Signal therapy for RAS induced cancers in combination of AG 879 and PP 1 , specific inhibitors for ErbB 2 and Src family kinases , that block PAK activation . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Various oncogenes ( e . g . ras , raf , neu , src , mos ) down regulate GJIC while several tumor suppressor genes can up regulate GJIC . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 phosphorylation induced by N . meningitidis provides docking sites for the kinase src and leads to its subsequent activation . ^^^ Specific inhibition of either ErbB 2 and / or src activity reduces bacterial internalization into endothelial cells without affecting bacteria induced actin cytoskeleton reorganization or ErbB 2 recruitment . ^^^ Altogether , our results provide new insight into ErbB 2 function by bringing evidence of a bacteria induced ErbB 2 clustering leading to src kinase phosphorylation and activation . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 activates Stat 3 alpha in a Src and JAK 2 dependent manner . ^^^ Both Src and Jak 2 kinases contribute to the activation of Stat 3 alpha but Src binds to ErbB 2 only when the receptor is phosphorylated . ^^^ Our results also suggest that tyrosine 1139 may be important for Src homology 2 domain association because a mutant lacking this tyrosine reduces the ability of the Src homology 2 domain to bind to ErbB 2 and significantly decreases its ability to activate Stat 3 alpha . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our previous studies demonstrated that Csk homologous kinase ( CHK ) acts as a negative growth regulator of human breast cancer through inhibition of ErbB 2 / neu mediated Src family kinase activity ( Bougeret , C . , Jiang , S . , Keydar , I . , and Avraham , H . ( 2001 ) J . ^^^ In this report , we investigated whether the interaction of the CHK SH 2 domain and ErbB 2 is directly related to the inhibition of heregulin stimulated Src kinase activity . ^^^ These new CHK high affinity binding constructs may serve as good candidates for inhibition of the ErbB 2 / Src transduction pathway in gene therapy studies in breast cancer . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Src overexpression was found to be frequently , but not always , associated with HER 2 / neu overexpression , but no statistical association between Src and Her 2 / neu overexpression could be demonstrated . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Thrombin phosphorylates EGFRs and ErbB 2 via a PP 1 sensitive pathway in PAR 1 ( / ) cells that stably overexpress PAR 4 ; the Src mediated pathway for EGFR / ErbB2 transactivation underlies the protracted phases of thrombin dependent extracellular signal regulated kinase activation in PAR 1 ( / ) cells that overexpress PAR 4 and in cardiomyocytes . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Finally , expression of the oncogenic activated ErbB 2 / Neu protein specifically enhanced ERalpha but not ERbeta interactions with SRC RIDs to an extent similar to E 2 stimulated interactions . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphatase epsilon activates Src and supports the transformed phenotype of Neu induced mammary tumor cells . ^^^ We show that at the molecular level , RPTPepsilon activates Src , a known collaborator of Neu in mammary tumorigenesis . ^^^ We conclude that RPTPepsilon is a physiological activator of Src in Neu induced mammary tumors and suggest that pharmacological inhibition of phosphatases that activate Src may be useful to augment direct pharmacological inhibition of Src . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| We examined the effect of protooncogenes of Cx 43 expression , and found no effect on Cx 43 promoter activity in cells transformed with Src or erbB 2 . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| EGFR , ErbB 2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene mediated transformation . ^^^ In this study , we show that H Ras , N Ras , K Ras , EGFR and ErbB 2 but not 5 Src suppress RhoB promoter transcriptional activity in NIH3T3 cells and human cancer cell lines derived from lung ( A 549 ) , pancreatic ( Panc 1 ) and cervical ( C33A ) tumors . ^^^ Ectopic expression of RhoB , but not the closely related family member RhoA , antagonizes the ability of EGFR , ErbB 2 , H Ras , N Ras and K Ras but not 5 Src to transform NIH3T3 cells . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Promising therapeutic targets for cancer metastasis have been identified , including Src , focal adhesion kinase , the integrin receptor , the vascular endothelial growth factor receptor , the epidermal growth factor receptor , Her 2 / neu , c Met , Ras / Rac GTPases , Raf kinase , farnesyl diphosphate synthase ( i . e . , amino bisphosphonate therapeutic target ) and matrix metalloproteases within the context of their implicated functional roles in cancer growth , invasion , angiogenesis and survival at secondary sites . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The transactivation of HER 2 / Neu by PGE ( 2 ) was inhibited by way of blocking the Src kinase signaling using the specific Src family inhibitor , PP 1 , or transfection with the mutant dominant negative src plasmid . ^^^ Src kinase was involved in not only the HER 2 / Neu transactivation but also the following VEGF C up regulation by PGE ( 2 ) treatment . ^^^ Taken together , our results provided evidence that COX 2 up regulated VEGF C and promotes lymphangiogenesis in human lung adenocarcinoma via the EP ( 1 ) / Src / HER 2 / Neu signaling pathway . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| We conclude that RPTP activates Src , Yes , and Fyn , but that these related kinases play distinct roles in Neu induced mammary tumor cells . . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Interestingly , pharmacological inhibition of the kinase activities of EGFR , erbB 2 , and src and activation of mitogen activated protein kinase , but not phosphatidylinositol 3 ' kinase , significantly up regulated SIRPalpha 1 promoter activity . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
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: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 promotes Src synthesis and stability : novel mechanisms of Src activation that confer breast cancer metastasis . ^^^ While investigating the signal transduction pathways contributing to ErbB 2 mediated metastasis , we found that ErbB 2 activated breast cancer cells that had higher metastatic potentials also had increased Src activity compared with ErbB 2 low expressing cells . ^^^ The increased Src activity in ErbB 2 activated cells paralleled higher Src protein levels , whereas Src RNA levels were not significantly altered . ^^^ Our studies revealed two novel mechanisms that are involved in Src protein up regulation and activation by ErbB 2 : ( a ) ErbB 2 increased Src translation through activation of the Akt / mammalian target of rapamycin / 4E BP 1 pathway and ( b ) ErbB 2 increased Src stability most likely through the inhibition of the calpain protease . ^^^ Furthermore , inhibition of Src activity by a Src specific inhibitor , PP 2 , or a Src dominant negative mutant dramatically reduced ErbB 2 mediated cancer cell invasion in vitro and metastasis in an experimental metastasis animal model . ^^^ |
|
| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| The interaction of Grb 7 with the ErbB 2 receptor is mediated via its Src homology 2 ( SH 2 ) domain . ^^^ |
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| Interacting proteins: P12931 and P04626 |
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 . . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| This review focuses on a discussion of tyrosine kinases thought to be important in disease , including platelet derived growth factor ( PDGF ) , fibroblast growth factor ( FGF ) , vascular endothelial cell growth factor ( VEGF ) , epidermal growth factor ( EGF ) receptors , HER 2 and Src . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that these protrusions result from a Rho and Cdc 42 dependent cortical actin polymerization , and from the activation of the ErbB 2 tyrosine kinase receptor and the Src kinase , leading to tyrosine phosphorylation of cortactin . ^^^ Moreover , although they efficiently recruit and activate ErbB 2 and Src , these mutants are defective in the recruitment and phosphorylation of cortactin . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Upregulation and activation of PKC alpha by ErbB 2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKC alpha and Src inhibitors . ^^^ Moreover , ErbB 2 mediated upregulation of urokinase type plasminogen activator receptor ( uPAR ) is reduced by either the PKCalpha inhibitor Go 6976 or the Src inhibitor PP 2 , and the combination of Go 6976 with PP 2 is superior to either agent alone in suppressing uPAR expression and cell invasion . ^^^ These results demonstrate that PKCalpha is critical for ErbB 2 mediated cancer cell invasion and provide valuable insights for current and future PKCalpha and Src inhibitor clinical trials . . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Finally , VEGF C secretion by MDA MB 231 cells was inhibited in the presence of kinase inhibitors for Her 2 / neu , Src and p 38 MAPK , indicating a requirement of these kinases for VEGF C synthesis . ^^^ |
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| Interacting proteins: P12931 and P04626 |
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 . ^^^ 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 effects of NRG 1Beta were prevented by a src inhibitor as well as an antibody to erbB 2 . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| We further demonstrate that one of these ER cofactors , SRC 1 , can relieve oestrogen repression of the ERBB 2 enhancer and conclude that these data fit with a model whereby the ER and the ERBB 2 enhancer compete for this limiting , non DNA binding cofactor . ^^^ Thus , in oestrogenic conditions SRC 1 preferentially binds to the ER which effectively sequesters it thereby reducing enhancer activity , but in antioestrogenic media the cofactor is released from the ER and is therefore available to activate the ERBB 2 enhancer . . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Expression of SRC 1 , AIB 1 , and PEA 3 in HER 2 mediated endocrine resistant breast cancer ; a predictive role for SRC 1 . ^^^ AIM : To determine whether insensitivity to endocrine treatment in HER 2 positive patients is associated with enhanced expression of coactivator proteins , expression of the HER 2 transcriptional regulator , PEA 3 , and coregulatory proteins , AIB 1 and SRC 1 , was assessed in a cohort of patients with breast cancer of known HER 2 status . ^^^ METHODS : PEA 3 , AIB 1 , and SRC 1 protein expression in 70 primary breast tumours of known HER 2 status ( HER 2 positive , n = 35 ) and six reduction mammoplasties was assessed using immunohistochemistry . ^^^ RESULTS : In primary breast tumours expression of PEA 3 , AIB 1 , and SRC 1 was associated with HER 2 status ( p = 0 . 0486 , p = 0 . 0444 , and p = 0 . 0012 , respectively ) . ^^^ In the HER 2 positive population , PEA 3 expression was associated with SRC 1 ( p = 0 . 0354 ) , and both PEA 3 and SRC 1 were significantly associated with recurrence on univariate analysis ( p = 0 . 0345 ; p < 0 . 0001 ) . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| Oestrogen receptor beta protein expression was associated with disease free survival ( DFS ) and inversely associated with the expression of HER 2 ( P=0 . 0008 and P < 0 . 0001 , respectively ) , whereas SRC 1 was negatively associated with DFS and positively correlated with HER 2 ( P < 0 . 0001 and P < 0 . 0001 , respectively ) . ^^^ |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P12931 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
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