| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Furthermore , tyrosine phosphorylation of p52Shc and p46Shc and subsequent formation of Shc / Grb2 complex were detected in breast cancer cells in which the p 185 tyrosine kinase is activated , indicating that p66Shc is not required for mediating the HER 2 / neu signaling pathway in breast cancer cells . . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Taken together with our findings indicating coupling of ErbB 2 to Shc , these data suggest the importance of an alternative signaling pathway in Delta 973 EGFR cells mediated by the formation of heterodimeric structures between the truncated EGFR and ErbB 2 , followed by coupling through Shc to Grb2 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Receptor activation in cells expressing phosphorylation defective mutants of Shc and erbB 2 kinase showed that receptor autophosphorylation , but not Shc phosphorylation , is required for redistribution of Shc proteins . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Also , the major tyrosine phosphorylated proteins that associate with Grb 2 in erbB 2 over expressing cancer cells appear to be erbB 2 and Shc . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Complexes were also detected between Shc and erbB 2 4 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Some of the Shc associated phosphoproteins ( EGFR , PDGFR , erbB 2 , Met , bcr abl , H 4 ret ) bound both the Shc and Grb 2 SH2 domains in vitro ; others ( p 175 ; p 70 p80 ) only the Shc SH 2 domain and yet others ( p 140 ) only the Grb 2 SH3 domains . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of Shc proteins and formation of Shc / Grb2 complex correlate to the transformation of NIH3T3 cells mediated by the point mutation activated neu . ^^^ PLC gamma , ras GAP and Shc have been proposed to be in vivo substrates for the neu encoded p185neu receptor tyrosine kinases . ^^^ We compared the tyrosine phosphorylation levels of PLC gamma , ras GAP and Shc in two NIH3T3 derived cell lines , transformed B 104 1 1 and non transformed DHFR / G8 cells in which point mutation activated and normal rat neu genes were transfected and expressed , respectively . ^^^ Furthermore , we observed that association with Shc was severely impaired by deletion of most of the major autophosphorylation sites of the point mutated neu . ^^^ The truncated neu product , however , fully retained its ability to transform NIH3T3 cells , induce Shc tyrosine phosphorylation and Shc / Grb2 complex formation . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Shc products are substrates of erbB 2 kinase . ^^^ Here we report that Shc products are substrates also of the erbB 2 kinase and form complexes with the erbB 2 product in intact cells . ^^^ In vitro , the bacterially expressed Shc SH 2 domain is sufficient to reconstitute the high affinity Shc / erbB 2 interaction . ^^^ The erbB 2 region required for Shc binding was narrowed down to the most COOH terminal 179 residues of gp185erbB 2 ; within this region , phosphorylation of one or more of the erbB 2 autophosphorylation sites is required for Shc / gp185erbB 2 complex formation as well as optimal phosphorylation of Shc products by the erbB 2 kinase . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| To clarify the role of the Shc Grb 2 Sos trimer in the oncogenic signaling of the point mutation activated HER 2 / neu receptor tyrosine kinase ( named p 185 ) , we interfered with the protein protein interactions in the Shc . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Shc dominant negative disrupts cell cycle progression in both G 0 G1 and G 2 M of ErbB 2 positive breast cancer cells . ^^^ We have shown that several breast cancer cell lines ( MDA MB 453 , BT 474 , MDA MB 361 , and SKBR 3 ) , which overexpress the ErbB 2 receptor tyrosine kinase , contain constitutively tyrosine phosphorylated Shc . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast , EGFR truncation did not impair EGF mitogenic signaling , and in c ' 1000 cells EGF was able to stimulate the association of ErbB 2 with GRB 2 and SHC . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| The 180 kDa Shc associated tyrosine phosphoprotein band contains both epidermal growth factor ( EGF ) receptor and p 185 ( neu ) . 3 5 fold increases in EGF receptor but not p 185 ( neu ) tyrosine phosphorylation occur following Gi coupled receptor stimulation . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast to p185erbB2 , p185erbB2 ( 5 E ) associated constitutively with members of the Shc protein family , leading to phosphorylation of Shc and to stimulation of mitogen activated protein kinase ( MAP kinase ) . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin was found to promote ErbB3 / Shc association in NIH 3T3 cells expressing endogenous ErbB 2 and recombinant ErbB 3 . ^^^ These results showed a specific interaction of Shc with the ErbB 3 receptor protein and demonstrated the importance of this interaction in the activation of mitogenic responses by the ErbB 2 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Constitutively tyrosine phosphorylated p 52 Shc in breast cancer cells : correlation with ErbB 2 and p 66 Shc expression . ^^^ To begin to test this prediction , we examined Shc tyrosine phosphorylation in a diverse group of breast cancer cell lines that display varied levels of ErbB 2 . ^^^ Using Shc immunoprecipitation and anti phosphotyrosine immunoblotting analysis , we found a strong correlation between the level of ErbB 2 overexpression ( r = 0 . 91 , p < 0 . 0002 ) and PY ErbB 2 levels ( r = 0 . 89 , p = 0 . 0005 ) compared with the level of tyrosine phosphorylation of the p 52 and p 46 Shc isoforms . ^^^ Consistent with Shc tyrosine phosphorylation being driven by ErbB 2 , an ErbB 2 specific tyrosine kinase inhibitor markedly reduced Shc tyrosine phosphorylation . ^^^ Unexpectedly , although all cell lines had comparable total amounts of p 52 and p 46 Shc , the amount of an inhibitory Shc isoform , p 66 , was inversely related to the level of ErbB 2 expression ( r = 0 . 86 , p = 0 . 0013 ) . ^^^ |
|
| Interacting proteins: P29353 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: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Transformation by overexpression of ErbB 2 correlated with ligand independent tyrosine phosphorylation of ErbB 2 and the adaptor protein Shc . ^^^ Over expression of ErbB 2 also resulted in the ligand independent constitutive association between Shc and another adaptor protein , Grb 2 , indicating that receptor activation was sufficient to activate downstream signalling pathways . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| ID 5 preferentially induced binding of the Mr 46 , 000 isoform of SHC to HER 2 , whereas heregulin preferentially induced binding of the Mr 52 , 00 isoform of SHC to HER 3 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Here we show that the oncogenic form of Neu is constitutively associated with the product of the c cbl proto oncogene and is part of a large complex that includes the phosphoinositide 3 kinase and Shc . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Collagen homology domain 1 deletion mutant of Shc suppresses transformation mediated by neu through a MAPK independent pathway . ^^^ To better understand the role of Shc in the oncogenesis by point mutation activated neu ( p185 * ) , we transfected a Shc mutant ( ShcdeltaCHI ) , which lacks the Grb 2 binding site Y 317 by deletion of collagen homology domain 1 , into p185 * transformed NIH3T3 cells . ^^^ Taken together , these data demonstrate that ShcdeltaCH 1 suppresses the transformation induced by activated neu through a MAPK independent pathway , indicating that Shc may be involved in other signal pathway ( s ) critical for cellular transformation in addition to the MAPK pathway . . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation of cell lysates with anti phosphotyrosine and immunoblotting showed phosphorylated forms of the mitogenic pathway proteins Shc and MAPK in addition to p 185 ( neu ) , suggesting that the Ras to MAPK mitogenic pathway is activated . ^^^ Immunoblotting of p 185 ( neu ) containing microvillar fractions revealed the presence in each of stably associated Shc , Grb 2 , Sos , Ras , Raf , mitogen activated protein kinase kinase , and mitogen activated protein kinase / extracellular signal regulated kinase , as well as the transcription factor phosphorylating kinase Rsk . ^^^ |
|
| Interacting proteins: P29353 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: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neuregulin increases the association of the adaptor proteins Grb 2 and Shc with both ErbB 2 and ErbB 3 in C2C12 muscle cells . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Breast carcinoma cells with HER 2 gene amplification ( 21 MT 1 cells ) and normal mammary epithelial cells without HER 2 gene amplification from the same patient ( H16N 2 cells ) were infected with pCMV dn 3 and assessed for HER 2 / HER 3 receptor tyrosine phosphorylation , p85PI 3 kinase and SHC protein activation , growth factor dependent and independent proliferation , and transformed growth in culture . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Grb 2 and Shc adapter proteins play distinct roles in Neu ( ErbB 2 ) induced mammary tumorigenesis : implications for human breast cancer . ^^^ To further address the significance of these ErbB 2 coupled signaling molecules in induction of mammary cancers , transgenic mice expressing mutant Neu receptors lacking the known autophosphorylation sites ( NYPD ) or those coupled directly to either Grb 2 ( YB ) or Shc ( YD ) adapter molecules were derived . ^^^ These observations argue that Grb 2 and Shc play important and distinct roles in ErbB 2 / Neu induced mammary tumorigenesis and metastasis . . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Although it interacts with the ErbB 2 C terminus through the PDZ domain , Erbin has no effect on ErbB 2 tyrosine phosphorylation or binding to the adaptor proteins Shc and Grb 2 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Suppression of ErbB 2 / Neu induced phenotypes in tissues haplosufficient for genes encoding adaptor protein or second messengers suggests that pTyr 1227 ( YD ) signals require Shc , and that pTyr 1253 ( YE ) signalling does not employ Ras , but does require Raf function . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| When crossed with mice expressing activated forms of the Neu receptor tyrosine kinase that selectively couple to the Grb 2 or Shc signaling pathways the activated type 1 receptor increased the latency of mammary tumor formation but also enhanced the frequency of extravascular lung metastasis . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Overexpression of ErbB 2 receptor inhibits IGF 1 induced Shc MAPK signaling pathway in breast cancer cells . ^^^ The inhibition of IGF 1 induced MAP kinase activation in ErbB 2 overexpressing breast cancer cells is correlated with decreased IGF 1 induced Shc tyrosine phosphorylation , leading to a decreased association of Grb 2 with Shc and decreased Raf phosphorylation . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| The Shc adaptor protein is critical for VEGF induction by Met / HGF and ErbB 2 receptors and for early onset of tumor angiogenesis . ^^^ Together , our findings identify Shc as a critical angiogenic switch for VEGF production downstream from the Met and ErbB 2 RTKs . . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| We describe a novel molecule , Memo ( mediator of ErbB 2 driven cell motility ) , that interacts with a phospho Tyr 1227 containing peptide , most probably through the Shc adaptor protein . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Stimulation of the duct cells with epidermal growth factor ( EGF ) and betacellulin results in Tyr phosphorylation of ErbB 1 and ErbB 2 , followed by activation of Shc , MEK1 / 2 and ERK1 / 2 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| In addition , 1 , 25D decreased tyrosine phosphorylation of HER 2 , an EGFR family member inactivated by PAcP , and the HER 2 downstream adaptor protein p 52 Shc in C 81 LN cells . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our results indicate that while there are measurable differences in the abilities of the two mutant receptors to stimulate [ ( 3 ) H ] thymidine incorporation between 20 and 24 h after addition of EGF , these differences can not be correlated with significant differences in EGF stimulated tyrosine phosphorylation of mutant EGF receptor and endogenous ErbB 2 , the extent of receptor internalization , EGF stimulated ion uptake , stimulation of SHC activity , or receptor association with Grb 2 . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , expression of Gab 2 mutated at this site ( S159A Gab 2 ) not only enhanced HRG induced Gab 2 tyrosine phosphorylation and association with Shc and ErbB 2 , but also markedly increased tyrosine phosphorylation of ErbB 2 and other cellular proteins and amplified activation of the ERK and PKB pathways . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| Crosslinking also decreased ErbB 2 ErbB3 heteroassociation and the EGF and heregulin induced tyrosine phosphorylation of Shc . ^^^ |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P29353 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|