| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.50833101 |
| Tyrosine phosphorylated IRS 1 bound and subsequently activated phosphatidylinositol 3 kinase by 3 . 5 fold , whereas the tyrosine phosphorylated IGF 1 receptor was not directly associated with the p 85 subunit of the phosphatidylinositol 3 kinase . 0.50833101^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :1.0058467 |
| We have used the yeast two hybrid system to study the interaction between the IGF 1 receptor and two putative substrates , IRS 1 and Shc . 1.0058467^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.88494653 |
| Using the yeast two hybrid system , a genetic assay for studying protein protein interactions , we have examined and compared the interaction of the insulin like growth factor 1 receptor ( IGF IR ) and the insulin receptor ( IR ) with their two known substrates p52Shc and the insulin receptor substrate 1 ( IRS 1 ) . 0.88494653^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.54929854 |
| We conclude that IRS 2 , unlike IRS 1 , can interact with tyrosine phosphorylated receptors such as the IR and insulin like growth factor 1 receptor via multiple independent binding motifs . 0.54929854^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.89047999 |
| A receptor binding assay based on the surface plasmon resonance ( SPR ) biosensor technique was developed to study the interaction between insulin like growth factor 1 receptor ( IGF 1R ) and its intracellular substrate protein insulin receptor substrate 1 ( IRS 1 ) . 0.89047999^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.57497136 |
| In this study we demonstrate that IRS 1 , SHC , and the p 85 subunit of phosphatidylinositol 3 kinase interact directly and specifically with the IGFIR . 0.57497136^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We identified insulin receptor substrate 1 ( IRS 1 ) as a common substrate for insulin and IGF 1 receptor tyrosine kinases . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In parallel , IGF 1 activates IGF 1 receptor , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 ( PI 3 ) kinase , and FAK . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Dephosphorylation of basal Ser / Thr sites on F IRS 1 also significantly reduced tyrosine phosphorylation by the IGF 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Expression of a human IGF 1 receptor in 32D / IRS 1 cells also results in nuclear translocation of IRS 1 and IL 3 independence . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| However , IGF 1 induced tyrosine phosphorylation of IGF 1 receptor and IRS 1 and AKT phosphorylation were unaffected by ErbB 2 overexpression . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| AIB 1 reduction decreased the expression of the IGF 1 receptor and IRS 1 in MCF 7 but not in MDA MB 231 cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| SH EP cells are glial like , express low levels of the type 1 IGF 1 receptor ( IGF IR ) and IRS 2 and high levels of IRS 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Transformation by the simian virus 40 T antigen is regulated by IGF 1 receptor and IRS 1 signaling . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| However , IGF 1 , IGF 1 receptor , and IRS 1 protein levels were induced by exposure to 25 mm glucose in both cell lines . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Moreover , the IGF IR and its two substrates , insulin receptor substrate 1 and SHC , were contained within the E cadherin complexes . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Neither the autophosphorylation of the IGF IR nor the tyrosyl phosphorylation of IRS 1 was affected by the expression of the MyCF plasmid . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Its major substrates , IRS 1 and Shc , determine whether the IGF IR will transform cells or will cause their differentiation . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Downstream of IGF IR , insulin receptor substrate 1 was phosphorylated , leading to the activation of phosphatidylinositol 3 ' kinase ( PI 3K ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In addition , IGF 1 induced IGF IR and insulin receptor substrate 1 phosphorylation were greatly impaired in ATM deficient cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Tumors from AS [ S ] ODN treated mice showed a decrease in IGF IR expression and in insulin receptor substrate 1 tyrosine phosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 promoted cholangiocyte proliferation in association with overexpression of p IGF1R , IRS 1 , IRS 2 , p ERK1 / 2 and p AKT . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| High concentrations of IGF 1 decreased levels of IGF IR and IRS 1 and inhibited the expression and activation of PDGFRalpha . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The effect of ethanol on IGF 1 receptor and insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation was determined by immunoprecipitation and Western blotting , as was the phosphatidylinositol 3 kinase content within IRS 1 immunoprecipitates . ^^^ CONCLUSIONS : The data indicate that physiologically relevant concentrations of ethanol inhibit the responses of glial cells to IGF 1 , including IGF 1 receptor autophosphorylation , IRS 1 and phosphatidylinositol 3 kinase activation , and cell growth . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Potentiation of IGF 1 action correlates with increased IGF 1 receptor associated phosphatidylinositol 3 kinase activity and tyrosine phosphorylation of Shc , but appears to be independent of activation of the IRS 1 / phosphatidylinositol 3 kinase signaling pathway . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Wheat germ agglutinin purified mutant receptors were as active in phosphorylating poly ( Glu , Tyr ) 4 : 1 as wild type IGF 1 receptors , suggesting that , in intact cells , additional factors are necessary in order for the IGF 1 receptor to phosphorylate IRS 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Insulin receptor substrate 1 ( IRS 1 ) is the major substrate of insulin receptor and IGF 1 receptor tyrosine kinases ; it has an apparent relative molecular mass of 160 190 , 000 ( M ( r ) , 160 190K ) on SDS polyacrylamide gel . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is the major substrate of insulin receptor and IGF 1 receptor tyrosine kinases ; it has an apparent relative molecular mass of 160 190 , 000 ( M ( r ) , 160 190K ) on SDS polyacrylamide gel . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IRS 1 has a central role as an adaptor molecule that links the insulin receptor and IGF 1 receptor kinases with enzymes that regulate cellular metabolism and growth . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Purified insulin receptor and IGF 1 receptor phosphorylated recombinant baculovirus produced IRS 1 on similar sites in vitro , and phosphorylated baculovirus produced IRS 1 bound PtdIns 3 ' kinase activity from lysates of quiescent cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Whereas only a small amount of PtdIns 3 kinase is found associated with the insulin and IGF 1 receptor , a considerable PtdIns 3 kinase activity is immunoprecipitated by an antibody raised against IRS 1 . ^^^ Since IRS 1 seems to be the connection between PtdIns 3 kinase and insulin or IGF 1 receptor , we used reconstitution experiments to characterize the implication of IRS 1 in the activation of PtdIns 3 kinase . ^^^ The interaction between PtdIns 3 kinase and IRS 1 phosphorylated by the insulin or the IGF 1 receptor results in the activation of PtdIns 3 kinase . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Xenopus oocytes from unprimed frogs possess insulin like growth factor 1 ( IGF 1 ) receptors but lack insulin and IGF 1 receptor substrate 1 ( IRS 1 ) , the endogenous substrate of this kinase , and fail to show downstream responses to hormonal stimulation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Insulin and IGF 1 receptors show distinct preferences for these peptides ; whereas insulin receptor prefers peptides based on Tyr 987 or Tyr 727 of insulin receptor substrate 1 , the IGF 1 receptor preferentially recognizes the Tyr 895 site . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In both cell lines , 25 mM glucose impaired receptor and insulin receptor substrate 1 phosphorylation by 34 % , but IGF 1 receptor phosphorylation was unaffected . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 receptor beta subunit , insulin receptor substrate 1 ( IRS 1 ) , and mitogen activated protein ( MAP ) kinase were all phosphorylated in response to 6 . 5 nM IGF 1 after 10 min incubation . ^^^ In contrast , the treatment with 23 nM TNF alpha failed to phosphorylate either IGF 1 receptor beta subunit or IRS 1 but did phosphorylate MAP kinase as much as IGF 1 did . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Our results strongly suggest that in human skin fibroblasts , which represent a more physiological cell culture : 1 ) IRS 1 , rather than Shc , is the major tyrosine phosphorylated protein binding GRB 2 in initial phase of IGF 1 signaling ; 2 ) mitogenic potency of receptor tyrosine kinases such as IGF 1 receptor and EGF receptor may not be determined solely by the amount of Shc GRB 2 complex or the activity of MAP kinase ; and 3 ) in contrast to previous reports , IGF 1 and EGF receptor signalings are not defective in leprechaunism . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Although TAM can increase IGFBP 3 expression in MCF 7 cells , and this binding protein has been shown to be able to inhibit IGF action , TAM had no effect on IGF 1 stimulated tyrosine phosphorylation of IGF 1 receptor or the downstream signaling molecule , insulin receptor substrate 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
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 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Two different beta subunits of IGF 1 receptor were detected , and their autophosphorylation was followed by increases in the phosphotyrosine content of extracellular signal regulated kinases ( ERKs ) , insulin receptor substrate 1 , phospholipase C gamma 1 , and phosphatidylinositol 3 kinase . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Furthermore , IGF 1 receptor tyrosine kinase activity was not affected by forskolin , suggesting that the increase in IRS 1 tyrosine phosphorylation was not the result of an increase in its activity . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| This study investigates the relationship between IGF 1 receptor internalization and signaling via IRS 1 and Shc . ^^^ A mutation in the C terminus of the IGF 1 receptor decreased both the rate of receptor internalization and IGF 1 stimulated Shc phosphorylation by more than 50 % , but did not affect IRS 1 phosphorylation . ^^^ These data support the concept that Shc / mitogen activated protein kinase pathway activation requires IGF 1 receptor internalization , whereas the IRS 1 pathway is activated by both cell surface and endosomal receptors . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In mammalian cells , the insulin receptor substrate 1 protein ( IRS 1 ) is a specific substrate for insulin and IGF 1 receptor tyrosine kinases which is involved in mediating metabolic and mitogenic actions of insulin and IGFs . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Both TCDD and BaP appeared to mimic signaling through the IGF 1 receptor ( IGF IR ) , as evidenced by increased tyrosine phosphophorylation of IGF IRbeta , IRS 1 and Shc . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| To determine whether blocking alphaVbeta 3 occupancy could alter IGF 1 receptor mediated signal transduction , the ability of IGF 1 to stimulate phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was analyzed . ^^^ We conclude that occupancy of the alphaVbeta 3 integrin is necessary for IGF 1 to fully activate the kinase activity of the IGF 1 receptor and phosphorylate IRS 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| This decrease in bioavailable IGF 2 ultimately resulted in diminished IGF 1 receptor signaling in vivo as evidenced by diminished receptor kinase activity and decreased tyrosine phosphorylation of the IGF 1 receptor downstream effectors , insulin receptor substrate 1 ( IRS 1 ) , extracellular signal regulatory kinase ( Erk ) 1 , and Erk 2 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The wild type insulin receptor chimera mediated approximately 2 fold greater phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , association of IRS 1 with phosphoinositide 3 kinase , stimulation of glucose uptake , and GLUT 4 translocation , compared with the IGF 1 receptor chimera . ^^^ We conclude that the insulin receptor mediates some aspects of metabolic signaling in adipocytes more effectively than the IGF 1 receptor , as a consequence of more efficient phosphorylation of IRS 1 and greater recruitment / activation of phosphoinositide 3 kinase . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Insulin like growth factor 1 ( IGF 1 ) dependent activation of pp42 / 44 mitogen activated protein kinase occurs independently of IGF 1 receptor kinase activation and IRS 1 tyrosine phosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Cell lines with the greatest degree of mutant IGF 1 receptor expression ( A / K cells ) demonstrated functional inactivation of endogenous IGF 1 receptors as determined by their impaired ability to phosphorylate the principal substrate of the IGF 1 receptor , IRS 1 , in response to treatment with IGF 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| LDL , in pathophysiological concentrations , affect the IGF 1 signaling pathway at multiple levels : 1 ) they induce phosphorylation of IGF 1 receptor beta and IRS 1 in a time and dose dependent manner ; 2 ) they up regulate IRS 1 associated PI 3 kinase / Akt activation in response to IGF 1 at early times ; and 3 ) they show additive effects with IGF 1 on extracellular signal regulated MAPK 1 / 2 phosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| They had phosphorylation of the IGF 1 receptor beta subunit , phosphorylation of insulin receptor substrate ( IRS ) 1 , and association of the p 85 subunit ( phosphatidylinositol 3 kinase [ PI3K ] ) with the IGF 1 receptor and IRS 1 in D NOD cells in the basal state . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Activation of the IGF 1 receptor also leads to phosphorylation of an 185 kDa molecule that is homologous to the substrate of the insulin receptor present in human cells , the insulin receptor substrate 1 ( IRS 1 ) . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| However , the levels of expression of IGF 1 receptor , or the activation of Insulin Receptor Substrate 1 in response to IGF 1 , were not affected by the levels of dlk expression . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Previous studies have suggested that antiestrogens inhibit MCF 7 cell proliferation by alteringthe expression or activity of components of the insulin like growth factor 1 ( IGF 1 ) signaling pathway , including IGF 1 receptor , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| TNF alpha and IL 1beta act by inhibiting the IGF 1 receptor from tyrosine phosphorylating insulin receptor substrate 1 without affecting tyrosine kinase activity of the IGF IR itself . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 ( 10 nM ) inhibited K ( + ) as well as veratridine evoked ACh release from rat hippocampal slices and the effect is possibly mediated via the activation of a typical IGF 1 receptor and the subsequent phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Preincubation with 1 mg / ml B IgG prevented insulin induced phosphorylation of insulin receptor and insulin receptor substrate 1 ( IRS 1 ) but did not alter the IGF 1 induced phosphorylation of the IGF 1 receptor and IRS 1 . ( 125 ) 1 insulin binding was inhibited by 93 % after preincubation with B IgG at 37 degrees C and was recovered up to 50 % of the control value by acid washing . ^^^ This effect of B IgG was specific for the insulin receptor with no effect on either IGF 1 receptor or IRS 1 , as reflected by the IGF 1 effectiveness on glycemic control in this patient . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Both medulloblastoma cell lines and medulloblastoma biopsies are characterized by the abundant presence of the IGF 1 receptor ( IGF IR ) and its major signaling molecule , insulin receptor substrate 1 ( IRS 1 ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| RESULTS : EtOH did not alter the total amount or tyrosine phosphorylation of the IGF 1 receptor , IRS 1 or PKB under basal or IGF stimulated conditions . ^^^ Furthermore , despite appropriate stimulation of IGF 1 receptor , IRS 1 and PKB , EtOH impairs IGF 1 signaling via S6K1 and 4E BP 1 pathways , and this defect is regulated in a glucocorticoid and TNF independent manner . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Genistein , biochanin A , quercetin and kaempferol reduced the insulin receptor substrate 1 ( IRS 1 ) content of AT6 . 3 cells and prevented the down regulation of IGF 1 receptor beta in response to IGF 1 binding . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In this paper we tested the hypothesis that polymorphic variants of IGF 1 response pathway genes , namely IGF IR ( IGF 1 receptor ; G / A , codon 1013 ) , PI3KCB ( phosphoinositol 3 kinase ; T / C , 359 bp ; A / G , 303 bp ) , IRS 1 ( insulin receptor substrate 1 ; G / A , codon 972 ) , and FOXO1A ( T / C , +97347 bp ) , play a role in systemic IGF 1 regulation and human longevity . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In terms of IGF 1 related second messenger proteins , the effect of thapsigargin is specific for IRS 1 since the protein levels of IGF 1 receptor beta subunit , Akt , Erk , and Shc are not affected . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We found that insulin receptor substrate 2 ( IRS 2 ) levels were markedly induced by progesterone and the synthetic progestin R 5020 in MCF 7 and other progesterone receptor ( PR ) positive breast cancer cell lines , whereas IRS 1 and the IGF 1 receptor were not induced . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| DCA induced activation of the insulin receptor correlated with enhanced phosphorylation of insulin receptor substrate 1 , effects that were both blocked by the insulin receptor inhibitor AG 1024 and by expression of the dominant negative IGF 1 receptor ( K1003R ) , which inhibited in trans . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In these protein kinase B / Akt 1 RNA interference cells , the signal molecules upstream of protein kinase B / Akt 1 , such as IGF 1 receptor and insulin receptor substrate 1 , were normally activated by insulin stimulation , whereas insulin stimulated phosphorylation of forkhead transcription factor ( FKHR ) , which is a downstream molecule of PKB / Akt 1 , was blocked . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The induced tumors showed upregulated expression of insulin receptor substrate 1 and phosphorylated forms of IGF 1 receptor and Akt , mimicking activated IGF signaling found in human MBs . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| EP 2 stimulation failed to inhibit tyrosine phosphorylation either of IGF 1 receptor or IRS 1 ( insulin receptor substrate 1 ) , or activation of phosphoinositide 3 kinase or Akt in response to IGF 1 , but potently and dose dependently inhibited IGF 1 induced activation of cellular Rac activity and membrane ruffling . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IRS 1 ( Insulin Receptor Substrate 1 ) is an adaptor protein important for insulin and IGF 1 receptor ( Insulin like Growth Factor IR ) transduction to downstream targets . ^^^ IRS 1 ( Insulin Receptor Substrate 1 ) is an adaptor protein important for insulin and IGF 1 receptor ( Insulin like Growth Factor IR ) transduction to downstream targets . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| These results indicate that IRS 1 ( activated by the IGF 1 receptor ) is one of several proteins that regulate the subcellular localization and activity of beta catenin . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 stimulated IGF 1 receptor activation was accompanied by recruitment of the adapter protein IRS 1 , activation of Erk1 / 2 , p70S6 kinase , and proliferation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Thus , mTOR inhibitors activate PI 3 K / AKT in multiple myeloma cells ; activation depends on basal IGF R signaling ; and enhanced IRS 1 / IGF 1 receptor interactions secondary to inhibited IRS 1 serine phosphorylation may play a role in activation of the cascade . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We measured insulin stimulated phosphorylation of the IR and IRS 1 , IRS 1 p 85 association and Akt activation , and the abundance of the IR , IRS 1 , p 85 , GLUT 4 and IGF 1 receptor in skeletal muscle . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Inhibition of CCN 6 expression promoted anchorage independent growth of HME cells and rendered them more responsive to the growth effects of IGF 1 , which was coupled with the increased phosphorylation of IGF 1 receptor and insulin receptor substrate 1 ( IRS 1 ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In these cells , the type 1 insulin like growth factor ( IGF 1 ) and granulocytic colony stimulating factor ( G CSF ) induce differentiation to granulocytes . 32D cells do not express insulin receptor substrate 1 ( IRS 1 ) or IRS 2 , docking proteins of the IGF 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| These abnormalities were associated reduced expression of genes encoding insulin , IGF 2 , insulin receptor , IGF 1 receptor , and insulin receptor substrate 1 , and reduced ligand binding to the insulin and IGF 2 receptors . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of IRS 1 in response to insulin was inhibited equally by blocking either the insulin or the IGF 1 receptor . ^^^ IRS 1 activation by AspB 10 insulin was only inhibited by blocking the IGF 1 receptor . ^^^ We conclude that in myoblasts IRS 2 , but not IRS 1 , functions as preferred substrate for the IGF 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Thrombin stimulates phosphorylation of insulin like growth factor 1 receptor , insulin receptor substrate 1 , and phospholipase C gamma 1 in rat aortic smooth muscle cells . ^^^ These proteins are insulin like growth factor 1 receptor beta subunit ( IGF IR beta ) , insulin receptor substrate 1 ( IRS 1 ) , and phospholipase C gamma 1 ( PLC gamma 1 ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We have recently shown that both SHC and IRS 1 interact with the tyrosine phosphorylated NPEY motif of the IR and insulin like growth factor 1 receptor via non SH 2 domains ( Gustafson , T . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The role of the insulin receptor substrate 1 ( IRS 1 ) in cellular transformation was studied in R cells , which are 3T3 like fibroblasts derived from mouse embryos with a targeted disruption of the insulin like growth factor 1 receptor gene . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The 5 ' region of the IRS 1 gene also has significant regions of homology with the promoters of the progesterone receptor gene , the insulin like growth factor 1 receptor gene , and the androgen receptor gene . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| G protein and tyrosine kinase receptor cross talk in rat aortic smooth muscle cells : thrombin and angiotensin 2 induced tyrosine phosphorylation of insulin receptor substrate 1 and insulin like growth factor 1 receptor . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Estradiol stimulates tyrosine phosphorylation of the insulin like growth factor 1 receptor and insulin receptor substrate 1 in the uterus . ^^^ Analysis of immunoprecipitates from uterine extracts revealed that E 2 enhanced tyrosine phosphorylation of the insulin like growth factor 1 receptor ( IGF 1R ) and insulin receptor substrate 1 ( IRS 1 ) by 6 hr . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Here , using two hybrid assays and in vitro assays of protein interaction , we show that the epsilon isoform of 14 3 3 interacts with the insulin like growth factor 1 receptor ( IGFIR ) and with insulin receptor substrate 1 ( IRS 1 ) , but not with the insulin receptor ( IR ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| To identify molecular defects responsible for this disease , we tested the implication of 14 candidate genes coding for proteins involved either in insulin action , i . e . insulin receptor , insulin receptor substrate 1 , insulin like growth factor 1 receptor , diabetes associated ras like protein ( Rad ) , and glycogen synthase , or in lipid metabolism , i . e . lipoprotein lipase ; apolipoproteins CII , AII , and CIII ; hepatic lipase ; hormone sensitive lipase ; the beta 3 adrenergic receptor ; leptin ; and fatty acid binding protein 2 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation experiments showed that insulin like growth factor 1 receptor and insulin receptor substrate 1 were tyrosine phosphorylated to the same extent in both cells treated with colchicine and in those not exposed to the drug . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Down regulation of insulin like growth factor 1 receptor and insulin receptor substrate 1 expression in advanced human breast cancer . ^^^ We investigated the expression pattern of insulin like growth factor 1 receptor ( IGF IR ) , insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) , a core downstream signaling protein , in 69 primary breast cancer specimens of different grades and in 21 control tissues by immunohistochemistry . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Estrogen can increase insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor substrate 1 ( IRS 1 ) expression , two key components of IGF 1 mediated signaling . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| ETV 6 NTRK 3 transformation requires insulin like growth factor 1 receptor signaling and is associated with constitutive IRS 1 tyrosine phosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In addition , the IRS 1 ( 925 1008 ) G972R peptide acted as a competitive inhibitor of insulin receptor and insulin like growth factor 1 receptor autophosphorylation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Insulin receptor substrate 1 ( IRS 1 ) transmits signals from the insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor ( IR ) and has been associated with the pathogenesis of cancer . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Surprisingly , T antigen does not operate directly , but utilizes insulin receptor substrate 1 ( IRS 1 ) , which is the major signaling molecule for insulin like growth factor 1 receptor ( IGF IR ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The aims of this study were to determine : ( 1 ) whether HCB is co carcinogenic in a medium term assay of N nitroso N methylurea ( NMU ) induced mammary tumors in rats ; ( 2 ) the effect of HCB on insulin receptor ( IR ) , insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor substrate 1 ( IRS 1 ) levels and on IRS 1 phosphorylation ; ( 3 ) microsomal and cytosolic Protein Tyrosine Kinase ( PTK ) activities in mammary glands and NMU induced tumors . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Mouse embryo cells expressing a wild type number of insulin like growth factor 1 receptors ( IGF IR ) ( W cells ) can be transformed either by simian virus 40 large T antigen ( SV 40 T ) or by overexpressed insulin receptor substrate 1 ( IRS 1 ) , singly transfected . ^^^ Neither SV 40 T antigen nor IRS 1 , individually , can transform mouse embryo cells with a targeted disruption of the IGF IR genes ( R cells ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In CHO cells stably increasing V922E IGF IR , both IRS 1 phosphorylation and the IRS 1 associated phosphoinositide 3 kinase activity were stimulated in the absence of IGF 1 to the level attained by 1 nM IGF 1 stimulation of wild type IGF IR , whereas the Ras mitogen activated protein kinase pathway was not activated under the same condition . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of both IGF IR and IRS 1 , either under basal conditions or after stimulation with growth factors , was strongly inhibited when alpha IR 3 , a monoclonal antibody to IGF IR , was added to the culture . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| However , both autophosphorylation of the IGF 1R beta subunit ( i . e . , IGF 1R tyrosine kinase ) and the IGF 1R tyrosine kinase activity towards exogenous insulin receptor substrate 1 , a natural substrate for IGF 1R tyrosine kinase , were reduced in CRF fats . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Although IRS 1 is the major substrate of the IGF IR , there is another early phosphotyrosine substrate termed SHC , which also activates Ras via Grb 2 mSos complex . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| A D amino acid analog of IGF 1 , JB 3 , inhibited SMC replication and dose dependently inhibited insulin receptor substrate 1 ( IRS 1 ) and IGF 1R phosphorylation in vitro . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF IR in transmitting signals to Shc and MAP kinase activation , which leads to decreased IGF 1 stimulated DNA synthesis , and that the kinase defective insulin receptor does not affect IGF 1 stimulated IRS 1 phosphorylation , which leads to the normal IGF 1 stimulated glycogen synthesis . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 stimulated autophosphorylation of the IGF IR and tyrosine phosphorylation of IRS 1 and SHC , known substrates in the IGF IR signal transduction pathway , were studied . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Consequently , we investigated how Tam modifies the IGF IR signaling pathway in estrogen receptor positive MCF 7 breast cancer cells and in MCF 7 derived clones overexpressing either the IGF IR ( MCF 7 / IGF IR cells ) or its major substrate , IRS 1 ( MCF 7 / IRS 1 cells ) . ^^^ MCF 7 / IGF IR and MCF 7 / IRS 1 cells exhibit greatly reduced estrogen growth requirements but retain estrogen receptors and express sensitivity to antiestrogens comparable to that in the parental cells . ^^^ The protein levels of the IGF IR and IRS 1 were not modified by Tam , whereas SHC protein expression was either not affected or moderately decreased by the treatment . ^^^ In summary , this work provides the first evidence that in MCF 7 cells , cytostatic effects of Tam are associated with the modulation of IGF IR signaling , specifically with : ( a ) down regulation of IGF 1 induced tyrosine phosphorylation of the IGF IR ; ( b ) inhibition of IRS 1 / phosphatidylinositol 3 ' kinase signaling ; and ( c ) up regulation of SHC tyrosine phosphorylation and increased SHC / GRB2 binding . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| When 32D cells are stably transfected with plasmids expressing either IRS 1 ( a major substrate of the IGF IR ) or the Simian virus 40 large T antigen , singly , they still undergo apoptosis after IL 3 withdrawal , although IRS 1 offers partial protection . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| To evaluate the function of 2 post receptor signaling molecules , insulin receptor substrate 1 ( IRS 1 ) ( a major substrate of the IGF IR ) and SHC ( a common substrate of tyrosine kinase receptors ) , we developed several MCF 7 derived cell clones in which the synthesis of either IRS 1 or SHC was blocked by antisense RNA . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| WF cells demonstrated a greater degree of ligand stimulated insulin receptor substrate 1 phosphorylation when compared with W cells , suggesting that expression of the EWS / FLI 1 fusion protein alters the IGF IR signaling pathway . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In 293 cells association of p55PIK with insulin receptor substrate 1 and with IGF IR was dependent on PI 3 kinase , since it was increased by wortmannin , an inhibitor of PI 3 kinase . ^^^ Importantly , this dominant negative mutant was more efficient than wild type p55PIK in associating to IGF IR and insulin receptor substrate 1 in 293 cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In conclusion , p 53 regulates IGF IR expression , as reflected by a reduction in IGF IR protein and a parallel reduction in IGF 1 induced tyrosine phosphorylation of the IGF IR and IRS 1 in an osteosarcoma cell line . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Estradiol also stimulated binding of IRS 1 and PI 3 kinase to the IGF 1R . ^^^ Depletion of IRS 1 from uterine extracts reduced PI 3 kinase associated with the receptor , which suggests that binding of the enzyme to IGF 1R occurs primarily in a complex that also contains IRS 1 . ^^^ Following treatment with estradiol , formation of Tyr ( P ) IGF 1R , Tyr ( P ) IRS 1 , and the p85 . ^^^ This indicated that most , if not all , of the estradiol stimulated Tyr phosphorylation of uterine IRS 1 originates from ligand activation of IGF 1R kinase . ^^^ In summary , our findings show that estrogen activation of uterine IGF 1R kinase results in enhanced binding of p 85 ( PI 3 kinase ) to IRS 1 and IRS 2 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Although the mitogenic function of the IGF IR may require the activation of insulin receptor substrate 1 ( IRS 1 ) or IRS 2 , an overexpressed IGF IR is able to protect 32D cells , which lack IRS 1 and IRS 2 , from apoptosis caused by Interleukin 3 ( IL 3 ) withdrawal . ^^^ Here , using mutational analysis , the authors identify domains of the IGF IR necessary to protect from apoptosis without downstream signaling from IRS 1 and IRS 2 . ^^^ Yet , overexpressed Shc and / or IRS 1 could not replace the IGF IR survival signal , suggesting the existence of other critical substrates . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| To this end we developed several MCF 7 clones that overexpressed insulin receptor substrate 1 ( IRS 1 ) , one of the principal substrates of the IGF IR . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Here , we studied the effects of ICI 182 , 780 on IGF IR signal transduction in MCF 7 breast cancer cells and in MCF 7 derived clones overexpressing either the IGF IR or its 2 major substrates , insulin receptor substrate 1 ( IRS 1 ) or src / collagen homology proteins ( SHC ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We find that one of the major substrates of the IGF IR , the insulin receptor substrate 1 inhibits IGF 1 mediated differentiation of 32D cells . ^^^ In the absence of insulin receptor substrate 1 , functional impairment of another major substrate of the IGF IR , the Shc proteins , is associated with a decrease in the extent of differentiation . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The IR , however , is not as efficient as the IGF IR in protecting mouse embryo fibroblasts from apoptosis , even when IRS 1 , one of its major substrates , is over expressed . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Most of its effects are mediated by the Type 1 IGF receptor ( IGF IR ) , a heterotetramer that has tyrosine kinase activity and phosphorylates insulin receptor substrates ( IRS 1 and 2 ) which leads to the activation of two downstream signaling cascades : the MAP kinase and the phosphatidylinositol 3 kinase ( P3K ) cascades . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Genetic ablation experiments of insulin receptor substrate 1 ( IRS 1 ) and 2 ( IRS 2 ) , two important molecules in the IR and IGF IR signaling pathways , are also beginning to shed light onto the mechanisms accounting for the specificity of IR and IGF IR signaling . ^^^ IRS 1 deficient mice are growth retarded , while IRS 2 deficient mice develop diabetes , indicating that the two molecules play a more specific role than previously recognized in IGF IR and IR signaling . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We report here that the vitamin D analogue EB 1089 interferes with the IGF IR signaling pathway by attenuating IGF 1 induced tyrosine phosphorylation of IRS 1 , and to a lesser extent , IRS 2 . ^^^ It does not affect protein levels of IRS 1 , IRS 2 or IGF IR . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In contrast , cell resistance to IGF 1 occurred at a step distal to IGF 1 receptors ( IGF IRs ) , as AIRs altered neither IGF 1 binding nor IGF 1 induced IGF IR autophosphorylation , but inhibited the ability of IGF IRs to mediate tyrosine phosphorylation of IRS 1 and IRS 2 in response to IGF 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In 32D cells ( a murine hemopoietic cell line devoid of insulin receptor substrate 1 [ IRS 1 ] ) , the IGF 1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin 3 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Ethanol inhibits IGF IR tyrosine autophosphorylation , which subsequently interferes with the activation of key downstream signaling mediators including insulin receptor substrate 1 , phosphatidylinositol 3 kinase , and mitogen activated protein ( MAP ) kinase . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The two major substrates of the IGF IR , insulin receptor substrate 1 ( IRS 1 ) and the Shc proteins , are known to contribute to this activation . ^^^ In the absence of IRS 1 , ERK activation is inhibited if the IGF IR is mutated at two domains : tyrosine Y 950 and a serine quartet at 1280 1283 . ^^^ Expression of IRS 1 in 32D cells expressing the double mutant IGF IR restores ERK activation . ^^^ The importance of the C terminus of the IGF IR in ERK activation ( in the absence of IRS 1 ) is confirmed by the failure of the insulin receptor to give a sustained activation of ERK . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Moreover , estrogens stimulate the expression of the IGF IR and its major signaling substrate IRS 1 , while antiestrogens downregulate IGF IR signaling , mainly by decreasing IRS 1 expression and function . ^^^ In ER negative breast cancer cells , usually displaying a more aggressive phenotype , the levels of the IGF IR and IRS 1 are often low and IGF is not mitogenic , yet the IGF IR is still required for metastatic spread . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In COS 7 cells , IGF 1 stimulation causes tyrosine phosphorylation of the IGF 1R beta subunit , the EGFR , insulin receptor substrate 1 ( IRS 1 ) , and the Shc adapter protein . ^^^ Tyrphostin AG 1478 , an inhibitor of the EGFR kinase , markedly attenuates IGF 1 stimulated phosphorylation of EGFR , Shc , and ERK1 / 2 but has no effect on phosphorylation of IGF 1R , IRS 1 , and protein kinase B ( Akt ) . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| After an initial burst of cell proliferation , the type 1 insulin like growth factor receptor ( IGF IR ) induces granulocytic differentiation of 32D IGF IR cells , an interleukin 3 dependent murine hemopoietic cell line devoid of insulin receptor substrate 1 ( IRS 1 ) . ^^^ The combined expression of the IGF IR and IRS 1 ( 32D IGF IR / IRS 1 cells ) inhibits IGF 1 mediated differentiation , and causes malignant transformation of 32D cells . ^^^ Because of the role of IRS 1 in changing the fate of 32D IGF IR cells from differentiation ( and subsequent cell death ) to malignant transformation , we have looked for differences in IGF IR signaling between 32D IGF IR and 32D IGF IR / IRS 1 cells . ^^^ A role of IRS 1 and p 70 ( S6K ) in the alternative between transformation or differentiation of 32D IGF IR cells was confirmed by findings that inhibition of p 70 ( S6K ) activation or IRS 1 signaling , by rapamycin or okadaic acid , induced differentiation of 32D IGF IR / IRS 1 cells . ^^^ We have also found that the expression of myeloperoxidase mRNA ( a marker of differentiation , which sharply increases in 32D IGF IR cells ) , does not increase in 32D IGF IR / IRS 1 cells , suggesting that the expression of IRS 1 in 32D IGF IR cells causes the extinction of the differentiation program initiated by the IGF IR , while leaving intact its proliferation program . . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| LNCaP prostatic cancer cells are characterized by having a PTEN mutation , low levels of type 1 insulin like growth factor receptor ( IGF IR ) and no IRS 1 , one of the major substrates of the IGF IR . ^^^ However , IGF IR signaling in the absence of IRS 1 can cause cell differentiation and growth arrest . ^^^ In support of this hypothesis , we report here that : ( 1 ) IRS 1 expression increases cell adhesion and decreases cell motility ; ( 2 ) over expression of the IGF IR , in the absence of IRS 1 , causes growth arrest and ( 3 ) a combination of IGF IR and IRS 1 restores the transformed phenotype of LNCaP cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Since Ras requires an active IGF 1R for transformation of fibroblasts , we asked whether expression of IRS 1 or Shc ( two of the major substrates of the IGF 1R ) could co operate with oncogenic Ras in transforming 32D cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Importantly , signaling molecules such as IGF IR , insulin receptor , and insulin receptor substrate 1 , leading to the MAP kinase pathway , were found to be concomitantly overexpressed within certain tumor lines , i . e . , MCF 7 and T 47D . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| It stimulated tyrosine phosphorylation of the type 1 IGF receptor ( IGF IR ) beta subunit , IRS 1 , IRS 2 , and Shc , and these changes were associated with activation of Erk and Akt . ^^^ PD 98059 inhibited activation of Erk and LY 294002 repressed activation of Akt in response to IGF 1 , but did not affect tyrosine phosphorylation of the IGF IR , IRS 1 , IRS 2 , or Shc . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Despite a significant reduction in levels of IGF 1R , IRS 1 , and IRS 2 phosphorylation , phospho p42 / p44 MAPK levels were only slightly decreased . ^^^ Basal phosphorylation of IGF 1R , IRS 1 , and p 85 subunit of PI 3K was decreased by tamoxifen . ^^^ Estradiol induced epithelial cell proliferation was associated with inhibition of IGFBP 3 gene expression , stimulation of IGFBP 2 gene expression , and increases in IGF 1R , IRS 1 , IRS 2 , and c Raf 1 levels . ^^^ Although basal phosphorylation of IGF 1R , IRS 1 , IRS 2 , Akt 1 , and the p 85 subunit of PI 3K was significantly increased by estradiol , basal phospho p44 / 42 MAPK was significantly reduced . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| H 19 7 / IGF IR cells have low levels of expression of insulin receptor substrate l ( IRS 1 ) , a major substrate of the IGF IR . ^^^ IGF 1 induces serine phosphorylation and down regulation of the endogenous IRS 1 upon differentiation of H 19 7 / IGF IR cells . ^^^ The profound influence of IRS 1 on differentiation of H 19 7 / IGF IR cells was confirmed by transfecting these cells with a plasmid expressing mouse IRS 1 . ^^^ Over expression of wild type IRS 1 in H 19 7 / IGF IR cells abolishes IGF 1 induced differentiation at 39 degrees C . ^^^ H 19 7 / IGF IR / IRS 1 cells at 39 degrees C show a stronger and prolonged activation of Akt , when compared to H 19 7 / IGF IR cells . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In estrogen receptor ( ER ) positive breast tumors , the levels of the IGF IR and its substrate , insulin receptor substrate 1 ( IRS 1 ) , are often elevated , and these characteristics have been linked with increased radioresistance and cancer recurrence . ^^^ In vitro , activation of the IGF IR / IRS 1 pathway in ER positive cells improves growth and counteracts apoptosis induced by anticancer treatments . ^^^ The impaired IGF 1 growth response of ER negative cells was not caused by a low IGF IR expression , defective IGF IR tyrosine phosphorylation , or improper tyrosine phosphorylation of IRS 1 . ^^^ |
|
| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Using Chinese hamster ovary ( CHO ) cells stably expressing human IR or IGF IR and activated by their respective ligands , we show that there are differences between the two receptors with regard to the complement of SH 2 containing proteins recruited to IRS 1 . ^^^ In particular , IGF IR appears to couple IRS 1 preferentially to Grb 2 whereas , in contrast , IR appears to couple IRS 1 preferentially to the p 85 subunit of phosphatidyl inositol 3 kinase ( PI 3 kinase ) and to Nck . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Upon insulin stimulation , tyrosine phosphorylation of ( insulin receptor substrate 1 ) IRS 1 was much higher in IGF IR ( / ) brown adipocytes , although IRS 1 protein content was reduced . ^^^ Downstream , the association IRS 1 / growth factor receptor binding protein 2 ( Grb 2 ) was augmented in the IGF IR ( / ) brown adipocyte cell line . ^^^ Finally , cells lacking IGF IR showed a much lower association between IR or IRS 1 and phosphotyrosine phosphatase 1B ( PTP1B ) and also a decreased PTP1B activity upon insulin stimulation . ^^^ Data presented here provide strong evidence that IGF IR deficient brown adipocytes show an increased insulin sensitivity via IRS 1 / Grb 2 / MAPK , resulting in an increased mitogenesis in response to insulin . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IRS 1 and Shc , substrates of the IGF IR , are known to mediate IGF IR signaling pathways such as those of mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 kinase ( PI3K ) , which are believed to play important roles in some of the IGF IR dependent biological functions . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 induced phosphorylation of IGF IR beta subunit , IRS 1 , mitogen activated protein kinase , Elk 1 , and Akt 1 as well as phosphatidylinositol 3 ' kinase activity was significantly attenuated when hepG 2 cells were pretreated with hrIGFBP 3 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Recent studies in a human cell line and a mouse model suggest that metastatic prostate cancer cell detachment may be favored by impairing cadherin function via loss of expression of insulin receptor substrate 1 ( IRS 1 ) , the principal IGF1R docking molecule . ^^^ We performed semiquantitative immunostaining for the IGF1R , IRS 1 , and PTEN , and in situ hybridization for IGF1R . ^^^ We also measured IGF1R , IRS 1 , and PTEN expression in 12 paired biopsies of primary prostate cancer and subsequent bone metastases . ^^^ In four cases , IGF1R and IRS 1 levels were lower in the metastases than in the primary tumors . ^^^ However , this pattern was relatively uncommon , and 8 of 12 cases expressed detectable IGF1R and IRS 1 in both primary and metastatic biopsies . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Results of this study show that the majority of cases examined were characterized by the abundant presence of the receptor for IGF 1 ( IGF IR ) protein ( 16 of 20 cases ) , and its major signaling molecule , insulin receptor substrate 1 ( IRS 1 ; 15 of 20 ) . ^^^ Protein levels for IGF IR and IRS 1 , determined by Western blot and immunohistochemistry , were significantly higher in medulloblastoma biopsies than in control cerebellar tissue . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Igf1r haploinsufficiency did not affect insulin action and compensatory beta cell growth in insulin resistant mice with combined Insr and Igf1r heterozygous null mutations , resulting in a considerably milder phenotype than combined haploinsufficiency for Insr and its main signaling substrates , Irs 1 and Irs 2 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF IR ( / ) cells showed an increased insulin sensitivity regarding insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation despite a substantial reduction in IRS 1 protein content . ^^^ Furthermore , insulin induced total and IRS 1 associated phosphatidylinositol 3 kinase activities were augmented in IGF IR deficient cells compared with wild type cells . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IRS 2 translocates to the nuclei of mouse embryo fibroblasts expressing the IGF IR , but , at variance with IRS 1 , does not translocate in cells expressing the Simian virus 40 T antigen . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We show here that insulin can also induce nuclear translocation of IRS 1 in mouse embryo fibroblasts ( MEF ) , that do not express the type 1 insulin like growth factor receptor ( IGF IR ) . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We investigated the effects of RA on the regulation of the IGF IR and its key signaling elements : IRS 1 , IRS 2 , and SHC . ^^^ To confirm the importance of IRS 1 regulation by RA , we examined the response to RA in MCF 7 cells overexpressing IGF IR and IRS 1 . ^^^ RA resistance was observed in MCF 7 cells overexpressing IRS 1 but not IGF IR . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Pre transfection of cultured hepatoma cells with p53mt249 resulted in a three to fourfold increase in IGF IR phosphorylation and downstream mediator IRS 1 phosphorylation but , enhanced more than 15 fold after IGF 2 treatment , which coincides well with the cell growth and thymidine uptake results . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 induced IGF 1R autophosphorylation ; IRS 1 phosphorylation and protein kinase B activation are inhibited at a low micromolar concentration range when applied to intact cells . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| IGF 1 rapidly and transiently induces association of IGF IR and beta 1 integrin , with phosphorylation of IGF IR , IRS 1 , and p 85 ( PI 3 K ) . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| This effect involves an interaction between Rad 51 and the major IGF IR signaling molecule , insulin receptor substrate 1 ( IRS 1 ) . ^^^ In the absence of IGF 1 stimulation , or if mutated IGF IR fails to phosphorylate IRS 1 , localization of Rad 51 to the sites of damaged DNA is diminished . ^^^ These results point to a direct role of IRS 1 in HRR and suggest a novel role for the IGF IR / IRS 1 axis in supporting the stability of the genome . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) , two major downstream molecules of IGF 1R , are known to be important in the genesis of diabetes . ^^^ Insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) , two major downstream molecules of IGF 1R , are known to be important in the genesis of diabetes . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Interestingly , autophosphorylation of the IGF IR and phosphorylation of the downstream substrate , insulin receptor substrate 1 ( IRS 1 ) , was not inhibited in doxycycline / IGF 1 treated cells , suggesting the possibility that activation of downstream substrates other than the IRS 1 may be critical for optimal cell proliferation . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The type 1 insulin like growth factor receptor ( IGF IR ) and its docking protein , insulin receptor substrate 1 ( IRS 1 ) , play important roles in cell transformation , cell differentiation and aging . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| In addition , CLA decreased IGF 1 induced phosphorylation of IGF IR and IRS 1 , recruitment of the p 85 subunit of phosphoinositide 3 kinase to IRS 1 and phosphorylation of Akt and extracellular signal regulated kinase 1 / 2 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The beta1A integrin forms a complex with the IGF IR and insulin receptor substrate 1 ( IRS 1 ) ; this complex does not promote IGF 1 mediated cell adhesion to laminin ( LN ) , although it does support IGF mediated cell proliferation . ^^^ Evidence is provided that the beta 1 cytodomain plays an important role in mediating beta 1 integrin association with either IRS 1 or Grb 2 associated binder 1 ( Gab 1 ) / SH2 containing protein tyrosine phosphate 2 ( Shp 2 ) , downstream effectors of IGF IR : specifically , beta1A associates with IRS 1 and beta1C with Gab1 / Shp2 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The partial differentialPHPTB IRS 2 is fully as capable as the wild type IRS 2 ( and wild type IRS 1 ) to stimulate the growth and inhibit the differentiation of 32D IGF IR cells . ^^^ In contrast , an IRS 1 protein lacking the same PH and PTB domains is completely inactive in blocking differentiation and stimulating IL 3 independent growth of 32D IGF IR cells . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Analysis of the IGF 1 transduction cascade demonstrated that the humanized anti IGF IR antibody and its murine parental form block IGF 1 induced tyrosine phosphorylation , both its beta chain and IRS 1 tyrosine phosphorylation . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Upon binding of IGF 1 or IGF 2 , IGF 1R , a tyrosine kinase , phosphorylates tyrosine residues on two major substrates , IRS 1 and Shc , which subsequently signal through the Ras / Raf and PI 3 kinase / AKT pathways ( 7 ) . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| These findings demonstrate that IGF IR signaling can increase the activity of UBF 1 and transcription from the rDNA promoter , providing one explanation for the reported effects of the IGF / IRS 1 axis on cell and body size in animals and cells in culture . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The growth and survival signals of IGF IR are mediated through multiple intracellular pathways , many of which emanate from insulin receptor substrate 1 ( IRS 1 ) . ^^^ In hormone dependent breast cancer cells , IGF IR and IRS 1 are often co expressed with the estrogen receptor alpha ( ERalpha ) , and IGF 1 and ER systems are engaged in a powerful functional cross talk . ^^^ Most notably , activation of ERalpha upregulates the expression of IRS 1 , IGF IR , and IGF 1 , which results in amplification of IGF 1 responses . ^^^ In contrast , in ERalpha negative breast cancer cells and tumors , the levels of IGF IR and IRS 1 are often decreased and IGF 1 is non mitogenic . ^^^ Our data suggest that defective IGF IR signaling in ERalpha negative cells is related , at least in part , to improper activation of the IRS 1 / PI 3K / Akt / GSK 3 pathway and lack of Rb 1 phosphorylation . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Levels of IRS 1 and IRS 2 were elevated in all tumours in the presence or absence of IGF IR , suggesting that the signalling pathway downstream of IGF IR is activated via IGF IR independent mechanisms in HCC . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| On ligand stimulation , IGF IR , a receptor tyrosine kinase , phosphorylates tyrosine residues on two major substrates , IRS 1 and Shc , which subsequently signal through the Ras / mitogen activated protein kinase and phosphatidylinositol 3 kinase / AKT pathways . ^^^ In addition to inhibiting IGF IR autophosphorylation , 19D12 also inhibits IRS 1 phosphorylation and activation of the major downstream signaling molecules AKT and extracellular signal regulated kinase 1 / 2 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| However , disruption of rafts by acute cholesterol depletion shifted IGF IR to non raft domains , abolished the IGF 1 mediated proapoptotic effect , and inhibited the IGF 1 dependent IRS 1 and Akt recruitment into and phosphorylation / activation within lipid rafts . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Coimmunoprecipitation studies demonstrated that IGF IR and insulin receptor substrate 1 associated with caveolin , a caveolar marker , in 3T3L1 and NWTb 3 cells . ^^^ Immunoblotting revealed that methyl cyclodextrin had no effect on IGF 1 induced activation of the IGF IR or insulin receptor substrate 1 but increased and decreased the phosphorylation of MAPK and protein kinase B , respectively . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The results showed that IGF 1 , IGF IR mRNAs , and phospho insulin receptor substrate 1 ( IRS 1 ) protein were decreased in ECC 1TAM compared with ECC 1E2 tumors . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| These results suggest that IGF 1 treatment prevents motor neuron loss by affecting the signal transduction system through IGF 1R and the main downstream signal , IRS 1 . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| We studied expression of the ligands IGF 1 and IGF 2 , the inhibitory IGF binding protein 3 , the type 1 IGF receptor ( IGF IR ) , and the downstream mediator insulin receptor substrate 1 by immunohistochemistry in 56 tissue specimens ( 28 low grade and 28 high grade prostate adenocarcinomas ) . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| The gene expression profile of TC / ET cells indicated , among up regulated genes , an increase in expression of insulin like growth factor receptor 1 ( IGF IR ) and one of its major intracellular mediators , insulin receptor substrate 1 . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism ( StAR , CYP 11 , CYP 17 , CYP 19 HSD17B1 3 , HSD3B1 2 ) , gonadotropin and gonadal hormones action ( ACTR 1 , ACTR2A B , FS , INHA , INHBA B , INHC , SHBG , LHCGR , FSHR , MADH 4 , AR ) , obesity and energy regulation ( MC4R , OB , OBR , POMC , UCP 2 3 ) , insulin secretion and action ( IGF 1 , IGF1R , IGFBPI 1 3 , INS VNTR , IR , INSL , IRS 1 2 , PPARG ) and many others . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation / western blot analyses revealed that genistein decreased IGF 1 stimulated phosphorylation of IGF IR and IRS 1 , recruitment of p 85 to IGF IR , and phosphorylation of Akt . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Since EN is known to bind IRS 1 as an adaptor protein , our findings suggest that IGF IR may function to localize EN / IRS 1 complexes to cell membranes , in turn facilitating PI3K Akt activation and suppression of anoikis . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Analyzing the signaling cascade initiated by IGF 1R , we observed a lack of IRS 1 induction in LIGFREKO livers . ^^^ Using the LIGFREKO model , we provide new evidence that IGF 1R / IRS 1 / ERK signaling may be the intracellular pathway controlling the cell cycle via cyclin D 1 and cyclin A in the regenerating liver . . ^^^ |
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| Interacting proteins: P08069 and P35568 |
Pubmed |
SVM Score :0.0 |
| Investigating the signaling pathway downstream of IGF 1R reveals that insulin receptor substrate 2 ( IRS 2 ) overexpression compensates for the lack of IGF 1R , whereas IRS 1 overexpression does not . ^^^ |
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