| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.71350067 |
| In this study , activation of the erbB 2 receptor and its association with Grb 2 and Sos was investigated in breast cancer cell lines which overexpress erbB 2 . 0.71350067^^^ The degree of association between the erbB 2 receptor and Grb 2 in vivo was related to erbB 2 overexpression , and MAP kinase , which functions downstream from Ras , displayed markedly increased activity in cell lines overexpressing erbB 2 . 0.69961532^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.77043487 |
| Against cultures of MDA MB 453 breast cancer cells , which over express erbB 2 tyrosine kinase , 8a is also antimitogenic at concentrations equivalent to those required to inhibit intracellular association of Grb 2 protein with phosphorylated p 185 ( erbB 2 ) protein ( IC ( 50 ) =8 microM ) . 0.77043487^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.85685196 |
| In whole cell studies using malonyl ethyl ester prodrug derivatives , it was observed that the 4 ( alpha hydroxymalonyl ) phenylalanyl containing peptide exhibited greater efficacy than the nonhydroxylated 4 ( malonyl ) phenylalanyl containing congener in blocking the association of Grb 2 with activated erbB 2 tyrosine kinase . 0.85685196^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have previously reported that the growth factor receptor bound protein 2 ( Grb 2 ) is required for the proliferation of ErbB 2 overexpressing breast cancer cells . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Further analyses indicate that the adaptor molecule , growth factor receptor bound protein 2 ( Grb 2 ) that is bound to p 185 ( HER 2 ) ( an oncogene product ) , is also associated with the CD44v3 Vav 2 complex . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast to EGF receptor and c erbB 2 , we were unable to detect binding of activated c erbB 3 to GRB 2 . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Dominant negative mutants of Grb 2 induced reversal of the transformed phenotypes caused by the point mutation activated rat HER 2 / Neu . ^^^ 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 . ^^^ Sos complex by introducing Grb 2 mutants with deletions in either amino ( delta N Grb 2 ) or carboxyl ( delta C Grb 2 ) terminal SH 3 domains into B 104 1 1 cells derived from NIH3T3 cells expressing the point mutation activated HER 2 / neu . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have examined Grb 2 protein interactions in human cancer cells that over express the receptor tyrosine kinase erbB 2 . ^^^ The Grb 2 SH3 domain interactions appear to be similar in erbB 2 over expressing breast , ovarian and lung cancer cells . ^^^ 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , GRb 2 was detected in erbB 2 and erbB 4 but not erbB 3 immunoprecipitates . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Phosphopeptide competition and site directed mutagenesis revealed that Tyr 1139 of erbB 2 is the major binding site for the Grb 7 SH2 domain , indicating an overlap in binding specificity between the Grb 7 and Grb 2 SH2 domains . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Following PMA induced tyrosine phosphorylation , ErbB 2 and ErbB 3 were able to associate with the SH 2 domains of several signaling proteins including the p85alpha subunit of phosphatidylinositol 3 kinase , Syp , and Grb 2 . ^^^ |
|
| Interacting proteins: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Growth inhibition of breast cancer cells by Grb 2 downregulation is correlated with inactivation of mitogen activated protein kinase in EGFR , but not in ErbB 2 , cells . ^^^ Grb 2 is important for the transformation of fibroblasts by EGFR and ErbB 2 ; however , whether Grb 2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear . ^^^ Grb 2 inhibition led to MAP kinase inactivation in EGFR , but not in ErbB 2 , breast cancer cells , suggesting that different pathways might be used by EGFR and ErbB 2 to regulate breast cancer growth . . ^^^ |
|
| Interacting proteins: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| 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: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Through its SH 2 domain , Grb 2 can constitutively associate with transmembranal PTPepsilon in mammary tumors initiated by ras or neu , and can be induced to associate with cytoplasmic PTPepsilon in Jurkat T cells following stimulation of T cell receptor signaling by pervanadate . ^^^ |
|
| Interacting proteins: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Pmf containing inhibitors show inhibition constants as low as 8 nM in extracellular Grb 2 binding assays and in whole cell systems , effective blockade of both endogenous Grb 2 binding to cognate erbB 2 , and downstream MAP kinase activation . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| By using a neutralizing antibody or dominant negative ( DN ) strategies or specific inhibitors , we also show that activation of Janus kinase Jak 2 by autocrine secretion of PRL is one of the significant components of constitutive tyrosine phosphorylation of ErbB 2 , its association with Grb 2 and activation of mitogen activated protein ( MAP ) kinase in human breast cancer cell lines that overexpress ErbB 2 . ^^^ Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB 2 by Jak 2 , provides docking sites for Grb 2 and stimulates Ras MAP kinase cascade , thereby causing unrestricted cellular proliferation . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast with full length tm PTPepsilon and cyt PTPepsilon , p 67 and p 65 are exclusively cytoplasmic , are not phosphorylated by Neu , and do not associate with Grb 2 in unstimulated cells . p 67 and p 65 are catalytically active and can reduce Src mediated phosphorylation of the Kv2 . 1 voltage gated potassium channel , albeit with reduced efficiency which most likely results from their cytoplasmic localization . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| The gene 33 protein may convey inhibitory signals downstream to ErbB 2 by virtue of its association with SH 3 containing proteins , including GRB 2 , which was found to associate with gene 33 protein in living cells . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neuregulin induced association of Sos Ras exchange protein with HER 2 ( erbB 2 ) / HER3 ( erbB 3 ) receptor complexes in Schwann cells through a specific Grb 2 HER2 ( erbB 2 ) interaction . ^^^ Far Western analysis indicates that Grb 2 and SOS bind exclusively to HER 2 in the HER2 / HER3 receptor complex . . ^^^ |
|
| Interacting proteins: P62993 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: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| We recently reported that GRB 2 does not link the HER 2 tyrosine kinase to the activation of ERK 1 , 2 but to another kinase , AKT . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| One of the critical intracellular signal transduction pathways involves the binding of the Grb 2 SH2 domain to the phosphotyrosine ( pTyr ) motifs on growth factor receptors , such as epidermal growth factor receptor ( EGFR ) and erbB 2 , leading to downstream activation of the oncogenic Ras signaling pathway . ^^^ |
|
| Interacting proteins: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| The most potent compound of the current study exhibited an IC ( 50 ) value of 0 . 002 microM in an extracellular ELISA based assay , and in MDA MB 453 cells , it both inhibited the association of Grb 2 with p 185 ( erbB 2 ) and exhibited antimitogenic effects with submicromolar IC 50 values . . ^^^ |
|
| Interacting proteins: P62993 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Whole cell assays indicate that peptide 20 can penetrate the cell membranes and inhibit the association of Grb 2 with p 185 ( erbB 2 ) in erbB 2 overexpressing MDA MA 453 cancer cells at low micromolar concentrations . . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| More significantly , both G1TE ( Gla ( 2 ) ) alone and the conjugate of G1TE ( Gla ( 2 ) ) with a peptide carrier can effectively inhibit intracellular association of erbB 2 and Grb 2 in the same cell lines with IC ( 50 ) of 50 and 2 microM , respectively . . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| In whole cell assays this novel analogue is able to effectively block the association of Grb 2 to cognate cytoplasmic erbB 2 at IC ( 50 ) < 10nM without prodrug derivatization or the addition of carrier peptide motifs . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| 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: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| Expression of erbB 2 and p Shc increased throughout treatment , whereas growth factor receptor binding protein 2 ( Grb 2 ) increased only in tumors proliferating on letrozole ( weeks 28 and 56 ) . ^^^ In cells isolated from tumors after 56 weeks and maintained as a cell line ( LTLT Ca ) in 1 micromol / L letrozole , ERalpha was also decreased whereas erbB 2 , adapter proteins ( p Shc and Grb 2 ) , and the signaling proteins in the mitogen activated protein kinase ( MAPK ) cascade were increased compared with MCF 7Ca cells . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| The phosphorylated ErbB 2 in CACO 2 cells recruits the cytoplasmic adaptor protein Grb 2 , consistent with previous studies showing phosphotyrosine 1139 to be a Grb 2 binding site . ^^^ |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|