| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.5675224 |
| C terminal Src kinase associates with ligand stimulated insulin like growth factor 1 receptor . 0.5675224^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.65470198 |
| IGF 2 promoted direct association of c SRC with IGF IR , phosphorylated c SRC , and increased EGFR phosphorylation at tyrosine 845 , a c SRC dependent phosphorylation site . 0.65470198^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| P2Y12 receptor signalling towards PKB proceeds through IGF 1 receptor cross talk and requires activation of Src , Pyk 2 and Rap 1 . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Involvement of Src homology / collagen ( SHC ) proteins in signaling through the insulin receptor and the insulin like growth factor 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Insulin like growth factor 1 receptor and insulin receptor association with a Src homology 2 domain containing putative adapter . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Insulin like growth factor 1 receptor activates c SRC and modifies transformation and motility of colon cancer in vitro . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| On the other hand Src activation through IGF IR is required for the cell proliferation , invasion , and also VPF / VEGF expression . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| We found that the beta subunit of the IGF 1 receptor comigrated on polyacrylamide gels with a component of the 95 kDa glycoprotein region from src transformed cells under both reducing and nonreducing gel conditions and had a very similar partial phosphopeptide map . ^^^ To further test the hypothesis that the beta subunit of the IGF 1 receptor becomes tyrosine phosphorylated in cells transformed by pp60src , a human cell line that expressed the IGF 1 receptor was transformed by src . ^^^ Comparison of IGF 1 receptors immunoprecipitated from normal and transformed cells revealed that the beta subunit of the IGF 1 receptor became constitutively tyrosine phosphorylated in src transformed cells . ^^^ Moreover , IGF 1 receptor phosphorylation induced by src was synergistic with that induced by the hormone : IGF 1 stimulated autophosphorylation of the receptor was much greater in src transformed cells than in untransformed HOS cells even at maximal concentrations of IGF 1 . ^^^ Our data demonstrate that the IGF 1 receptor becomes constitutively tyrosine phosphorylated in src transformed cells . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| IGF 1 receptor in src transformed cells . ^^^ It has not been clear , however , whether src induced phosphorylation altered the enzymatic or signaling properties of the IGF 1 receptor and thus whether the IGF 1 receptor could be a functionally significant target for pp60v src . ^^^ To examine the effect of src expression on the activity of the IGF 1 receptor , the human IGF 1 receptor was expressed in Rat 1 fibroblasts co expressing the temperature sensitive 5 src mutant , tsLA 29 . ^^^ The IGF 1 receptor exhibited an elevated level of tyrosine phosphorylation in src transformed cells even in the absence of IGF 1 treatment . ^^^ A kinase defective mutant of the IGF 1 receptor also became constitutively phosphorylated in src transformed cells , ruling out a possible autocrine mechanism for this phosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| The catalytic activity of IGF 1 receptor is stimulated approximately 3 . 4 fold by treatment with purified 5 Src , while insulin receptor shows very little effect of Src phosphorylation under these conditions . ^^^ This observation is relevant to recent findings of IGF 1 receptor activation in Src transformed cells , and may represent one method by which Src amplifies its mitogenic signal . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| The goal of the present study was to analyze the mechanistic basis and functional significance of the Src induced phosphorylation and activation of the IGF 1 receptor . 1 ) We mapped the sites of IGF 1 receptor autophosphorylation to peptides representing three different receptor domains : tyrosines 943 and 950 in the juxtamembrane region ; tyrosines 1131 , 1135 , and 1136 within the kinase domain ; and tyrosine 1316 in the carboxyl terminal domain . ^^^ The carboxyl terminal site , although phosphorylated in vitro and in src transformed cells , was not a major site of ligand induced phosphorylation in vivo . 2 ) We determined that the sites of Src induced phosphorylation of the IGF 1 receptor are the same as the ligand induced autophosphorylation sites and that the Src kinase can catalyze these phosphorylations directly . 3 ) We showed that cells cultured from mice in which the IGF 1 receptor has been knocked out by homologous recombination are defective for morphological transformation by src . ^^^ Thus , the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF 1 receptor , and this receptor phosphorylation and activation are essential for transformation by src . . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Although 5 src is a more potent inducer of tyrosine phosphorylation than c src 527 , the extent of phosphorylation of either insulin receptor substrate 1 or Shc , two of the major substrates of the IGF 1 receptor , does not seem sufficiently different to explain the qualitative difference in soft agar growth . 5 src , however , is considerably more efficient than c src 527 in its ability to tyrosyl phosphorylate , in R cells , the focal adhesion kinase , Stat 1 , and p130cas . ^^^ These results indicate that 5 src , but not c src 527 , can bypass the requirement for a functional IGF 1 receptor in the full transformation of mouse embryo fibroblasts and suggest that qualitative and quantitative differences between the two oncogenes can be used to identify some of the signals relevant to the mechanism ( s ) of transformation . . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Src stimulates insulin like growth factor 1 ( IGF 1 ) dependent cell proliferation by increasing IGF 1 receptor number in human pancreatic carcinoma cells . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Weakening of cell matrix adhesion is blocked significantly ( p < 0 . 01 ) by the catalytically inactive IGF 1 receptor ( IGF IR ) and the phosphoinositide 3 kinase ( PI 3 kinase ) inhibitor LY 294002 , but it is unaffected by mitogen activated protein kinase kinase inhibitor UO 126 and Src kinase inhibitor PP 2 . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| This inhibitory activity copurifies with the IR on insulin Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR related insulin like growth factor 1 receptor and the oncoprotein 5 abl but is ineffective against c src tyrosine kinase activity . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Increased tyrosine phosphorylation of these proteins is also observed in cells expressing a transforming chicken c Src ( mutant Phe 527 ) and in cells with the activated tyrosine kinase domains of the Drosophila insulin receptor , human insulin like growth factor 1 receptor , and human insulin receptor related receptor . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Cloning , chromosome localization , expression , and characterization of an Src homology 2 and pleckstrin homology domain containing insulin receptor binding protein hGrb10gamma . hGrb10alpha ( previously named Grb IR ) is a Src homology 2 domain containing protein that binds with high affinity to the tyrosine phosphorylated insulin receptor and insulin like growth factor 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Grb 10 interacts differentially with the insulin receptor , insulin like growth factor 1 receptor , and epidermal growth factor receptor via the Grb 10 Src homology 2 ( SH 2 ) domain and a second novel domain located between the pleckstrin homology and SH 2 domains . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| CONCLUSIONS : Preliminary studies have implicated , among others , the insulin like growth factor 1 receptor , Src , and Stat 3 proteins in human pancreatic carcinogenesis . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Here we investigate the requirement of MAP ( MAPK ) and phosphatidylinositol 3 ( PI3K ) kinases in the transformation of rat intestinal epithelial ( RIE ) cells by oncogenic forms of insulin receptor ( gag IR ) , insulin like growth factor 1 receptor ( gag IGFR ) , and 5 Src . ^^^ |
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| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Modification of insulin like growth factor 1 receptor , c Src , and Bcl XL protein expression during the progression of Barrett ' s neoplasia . ^^^ Among these , insulin like growth factor 1 receptor ( IGF 1 R ) and c Src are reported to be key regulators of mitogenesis and tumorigenesis . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Since thrombin rapidly activated Src in VSMC , Src may be involved in the cross talk between the G protein coupled receptor agonist and a tyrosine kinase receptor such as IGF 1R . . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| The activation of overexpressed wild type IGF IR , but not that of an ATP binding mutant of IGF IR , resulted in the increased tyrosine phosphorylation of several intracellular proteins , including SHC , Src homology 2 containing inositol 5 phosphatase , protein kinase C delta , and Erk 2 . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Src kinase inhibitors pyrazolopyrimidine PP 1 and PP 2 inhibited transactivation of the IGF IR by EGF . ^^^ EGF stimulated the tyrosine phosphorylation of Src , and induced its association with the IGF IR . ^^^ In conclusion , the data show an EGF and Src mediated transactivation pathway for IGF IR activation in hepatocytes , and indicate a role for the IGF IR in hepatocyte intracellular signaling . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Likewise , overexpression of a Grb 10 mutant lacking the Src homology 2 ( SH 2 ) domain impaired ubiquitination of the IGF IR in parental p 6 and p6 / Grb10 cells , indicating that Grb 10 binding to Nedd 4 is critical for ubiquitination of the receptor . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| When IGF 1 was added to cells expressing mutant beta 3 , SHP 2 was not recruited to the Src homology 2 domain containing tyrosine phosphatase substrate 1 or to IGF IR . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Src homology 2 / alpha collagen related protein ( Shc ) is the main mediator of IGF 1 mitogenic action , coupling IGF IR phosphorylation to Ras MAPK activation . ^^^ |
|
| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Coexpression of IGF 1R and c Src proteins in human pancreatic ductal adenocarcinoma . ^^^ It has been postulated that c Src may induce transformation by causing the overexpression of the insulinlike growth factor 1 receptor ( IGF 1R ) in pancreatic tumor cell lines . ^^^ To further study the interaction between c Src and IGF 1R proteins in human pancreatic cancer , we examined their coexpression in 47 human pancreatic ductal adenocarcinomas ( PDA ) . ^^^ We used an anti human IGF 1R mouse monoclonal antibody ( dilution 1 : 100 with antigen retrieval ) , and an anti c Src mouse monoclonal antibody ( dilution 1 : 100 with antigen retrieval ) . ^^^ Interestingly , in 40 / 47 ( 85 % ) cases c Src and IGF 1R stains had similar scores . ^^^ |
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| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| While Akt kinase is both necessary and sufficient to induce IGF IR upregulation , c Src kinase activity is necessary , but alone is insufficient to upregulate IGF IR expression . ^^^ |
|
| Interacting proteins: P08069 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 . ^^^ |
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| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Moreover , androgen induced IGF IR up regulation involves the activation of the Src extracellular signal regulated kinase pathway , because it was inhibited by both the Src inhibitor PP 2 and the MEK 1 inhibitor PD 98059 . ^^^ |
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| Interacting proteins: P08069 and P12931 |
Pubmed |
SVM Score :0.0 |
| Functional blocking monoclonal antibody against integrins alpha ( 5 ) beta 3 , but not alpha 2 alpha3 , alpha 4 alpha6 beta 1 , beta 4 or alpha2beta1 , inhibited the IGF 1 stimulated invasion and proliferation in cervical cancer cells . alpha ( 5 ) beta 3 integrin modulated IGF 1R phosphorylation by altering the rate of Src homology 2 containing phosphotyrosine phosphatase ( SHP 2 ) recruitment to the activated IGF 1R . ^^^ |
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