| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.78704038 |
| Shc physically interacts with IGF 1R in the plasma membrane , and E 2 activates IGF 1R . 0.78704038^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :1.0454381 |
| IGF 1 receptor binds to its ligand and activates two intracellular processes mainly a Shc mediated pro mitotic pathway and an anti apoptotic pathway mediated by IRS and Akt . 1.0454381^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.80972204 |
| It is possible that Shc and insulin receptor substrate ( IRS ) 1 can interact competitively , via their phosphotyrosine binding ( PTB ) domains , with the activated IGF 1 receptor . 0.80972204^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.91457809 |
| 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 ) . 0.91457809^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.70768643 |
| The interaction of all three proteins is dependent upon IGFIR kinase activity and , furthermore , substitution of Tyr 950 with Phe within the NPEY motif of the IGFIR eliminated interaction with both SHC and IRS 1 but had no effect upon p 85 interaction . 0.70768643^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.63714282 |
| Full length Shc was phosphorylated on tyrosine when coexpressed with IGFIR beta but not when coexpressed with the kinase negative receptor mutant . 0.63714282^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| These effects are mediated by changes in tyrosine phosphorylation of IGF 1 receptor substrates , including IRS 2 and Shc . . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Estradiol causes phosphorylation of the adaptor protein , Shc and the IGF 1 receptor itself . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| 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 P29353 |
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 P29353 |
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 . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Shc , one of the two major docking partners of IGF IR , is equally expressed in N and S cell lines . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| Downstream from Ras , IGF 1 increased both Raf kinase and protein kinase C ( PKC ) zeta activities by 3 . 5 fold . ( Bu ) 2cAMP , an inhibitor of IGF 1 induced mitogenesis in fetal brown adipocyte primary cultures , did not block the very early steps of the IGF 1 induced mitogenic cascade , such as IGF 1 receptor autophosphorylation , IRS 1 or SHC tyrosine phosphorylation , and Ras activation to its GTP active form . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
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 P29353 |
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 . ^^^ Low temperature ( 15 degrees C ) decreased IGF 1 receptor internalization and completely inhibited Shc 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 P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| In contrast , the IGF 1 receptor chimera mediated more effective Shc phosphorylation , association of Shc with Grb 2 , and activation of mitogen activated protein kinase compared with the insulin receptor chimera . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| In order to gain further insight into IGF 1 receptor signaling in Xenopus laevis oocytes and embryos , we have undertaken the characterization of the adapter protein Shc and studied its implication in oocyte maturation induced after IGF 1 receptor activation , especially since expression of this molecule has been indirectly evidenced in Xenopus oocytes , eggs and embryos . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| Since 1996 , seven genetic mouse models have been reported to show increased lifespan : Ames and Snell dwarf mice , the ' little mouse ' ( Ghrhr ( lit / lit ) ) , mice null for either growth hormone receptor / binding protein ( GHR / BP ( / ) ) or p 66 ( shc ) ( p 66 ( shc / ) ) , mice heterozygous for the IGF 1 receptor ( Igf1r ( + / ) ) , and fat specific insulin receptor knockout mice . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Targeted mutations that affect components of this pathway , including the GH receptor , p66Shc , and the IGF 1 receptor ( IGF 1R ) , also extend life span ; mutations that affect IGF 1R or downstream components of the pathway decouple longevity effects from dwarfism . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| We briefly compare calorie restriction , GHRH R and Pit 1 mutants with knockout phenotypes of GH receptor , IGF 1 receptor and p66Shc , to make some general conclusions . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Moreover , it was recently suggested that p66Shc , which is an adaptor molecule of the IGF 1 receptor , might play a critical role in this synergistic effect . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Resistance to oxidative stress in these mutant animals could be caused by decreased phosphorylation of molecules downstream of the IGF 1 receptor in the IGF 1 signalling pathway , one of which is thought to be p66shc . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| Transient expression of Vav in 293T and NIH 3T3 cells demonstrated that ligand stimulation of several RPTKs ( epidermal growth factor receptor [ EGFR ] , Ros , insulin receptor [ IR ] , and insulin like growth factor 1 receptor [ IGFR ] ) led to tyrosine phosphorylation of Vav 3 and its association with the receptors as well as their downstream signaling molecules , including Shc , Grb 2 , phospholipase C ( PLC gamma ) , and phosphatidylinositol 3 kinase . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Role of the p66Shc isoform in insulin like growth factor 1 receptor signaling through MEK / Erk and regulation of actin cytoskeleton in rat myoblasts . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| The same antibody to SV 40 T antigen , however , fails to coprecipitate another substrate of IGF IR , the transforming protein Shc , and two other signal transducing molecules , Grb 2 and Sos . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild type IGF IR in Asp 1048 IR cells . ^^^ 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 P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| In contrast , under the same treatment , tyrosine phosphorylation of Src homology / collagen proteins ( SHC ; another substrate of the IGF IR ) and SHC / GRB2 binding were elevated . ^^^ 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 P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| Both chIR and IGF IR exhibit comparable levels of enzymatic activity as evidenced by their ability to autophosphorylate and transphosphorylate the shc protein in vivo . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
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 . ^^^ IL 4 stimulation of the IGF IR transfectants resulted in enhanced tyrosine phosphorylation of SHC , Erk 2 , and signal transducer and activator of transcription 6 ( STAT 6 ) proteins . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| 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 P29353 |
Pubmed |
SVM Score :0.0 |
| Moreover , exposure of collagen type 2 cultured chondrocytes to IGF 1 leads to co immunoprecipitation of Shc protein with the IGF IR and with beta 1 , alpha 1 and alpha 5 integrins , but not with alpha 3 integrin . ^^^ Thus , the collagen binding integrins and IGF IR co operate to regulate focal adhesion components and these signalling pathways have common targets ( Shc Grb 2 complex ) in subcellular compartments , thereby linking to the Ras mitogen activated protein kinase signalling pathway . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 . ^^^ Shc immunoprecipitates performed after IGF 1 stimulation contain coprecipitated EGFR , suggesting that IGF 1R activation induces the assembly of EGFR . ^^^ 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 P29353 |
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 P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| Functional studies demonstrated that insulin induced a dose dependent phosphorylation of the insulin receptor , IGF 1R , insulin receptor substrates 1 and 2 , Shc , and STAT 1 . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| The tyrosine phosphorylation of IGF IR , IRS 2 , Shc , and p42 / p44 MAP kinase ( MAPK ) , and the association of Grb 2 with Shc , were examined by immunoprecipitations and Western blotting . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation of both receptor forms by antibodies against the alpha subunit and against the carboxy terminus of the beta subunit of the IGF IR suggests that the 75 kDa form could be the beta chain truncated at the amino terminus above the alpha beta disulphide bridges . 3 ) The ATA activated IGF IR forms underwent slow dephosphorylation , compared with a rapid dephosphorylation of the IGF 1 activated receptor . 4 ) The insulin receptor substrate 1 / 2 associated PI3K , Shc proteins , and the kinases Akt and Erk1 / 2 , downstream mediators of the antiapoptotic signaling by IGF IR , were activated to a higher extent and for a longer time period by ATA , compared with IGF 1 . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
Pubmed |
SVM Score :0.0 |
| However , SHC expression and SHC tyrosine phosphorylation and its association with Grb 2 were unaltered in response to insulin in IGF IR deficient brown adipocytes . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 P29353 |
Pubmed |
SVM Score :0.0 |
| These IGF1R ( + / ) mutants were also more resistant to oxidative stress in vivo , and we identified a possible molecular pathway linking underphosphorylation of IGF 1 receptors to the lack of activation of p66Shc , a protein capable of increasing resistance to oxidative stress through regulation of a set of downstream genes . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 ) . ^^^ |
|
| Interacting proteins: P08069 and P29353 |
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 . ^^^ |
|