| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.64802377 |
| Activation of PI3K by glucose dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate 2 and growth factor bound 2 associated binder 1 and PI3K isoforms p85alpha , p110alpha , p110beta , and p110gamma . 0.64802377^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.9339016 |
| Similar to cells expressing full length receptor , PI3K was activated by its incorporation into a complex with IRS 2 or Gab 2 . 0.9339016^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Muscle abundance of IRS 2 and p 85 subunit of PI3K were unaltered by diet , but IRS 1 content was lower in CR vs . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| This pathway involves stimulation of phosphatidylinositol 3 kinase ( PI3K ) binding to insulin receptor substrate 1 and insulin receptor substrate 2 , activation of PI3K and protein kinase B ( AKT ) , and PI3K dependent activation of cyclic nucleotide phosphodiesterase 3B , a cAMP degrading enzyme . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Although a direct association between PI3K and Mpl could not be demonstrated , we found that several proteins , including SHP 2 , Gab 2 , and IRS 2 , undergo phosphorylation and association in BaF3 / Mpl cells in response to TPO stimulation , complexes that recruit and enhance the enzymatic activity of PI3K . ^^^ In primary murine MKs , TPO also induced phosphorylation of SHP 2 , its association with p 85 and enhanced PI3K activity , but in contrast to the results in cell lines , neither Gab 2 nor IRS 2 are phosphorylated in MKs . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Furthermore , E 2 induced diminution of uterine insulin receptor substrate 2 protein was only partially inhibited in the presence of wortmannin , a PI3K inhibitor . ^^^ Collectively , these data suggest that the E 2 induced decrease in uterine insulin receptor substrate 2 requires IGF 1 signaling , is not dependent solely on insulin receptor substrate 1 and PI3K , and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Similar to TNF , cycloheximide and anisomycin stimulated serine phosphorylation of IRS 1 and IRS 2 , reduced their ability to interact with the insulin receptor , inhibited the insulin induced tyrosine phosphorylation of IRS proteins , and diminished their association with phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Insulin stimulation of insulin receptor substrate ( IRS ) 1 , IRS 2 , and antiphosphotyrosine associated phosphatidylinositol 3 kinase ( PI3K ) was similar for CR and AL . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Thus , a prolonged activation of Erk1 / 2 and PI3K signaling pathways is important in committing a beta cell to a mitogenic event , and it is likely that this sustained activation is instigated by signal transduction occurring specifically through IRS 2 . . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Cbl , IRS 1 , and IRS 2 mediate effects of rosiglitazone on PI3K , PKC lambda , and glucose transport in 3T3 / L1 adipocytes . ^^^ Additionally , rosiglitazone increased IRS 1 and IRS 2 levels , thereby enhancing insulin effects on IRS 1 and IRS 2 dependent PI3K and downstream signaling factors PKC lambda and protein kinase B . ^^^ Our findings suggest that Cbl participates in mediating effects of rosiglitazone on PI3K , PDK 1 , and PKC lambda and the glucose transport system and that this Cbl dependent pathway complements the IRS 1 and IRS 2 pathways for activating PI3K , PDK 1 , and PKC lambda during combined actions of rosiglitazone and insulin in 3T3 / L1 cells . . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| These include a decreased IRS 2 pool level , a decrease in PI3K activity and its association with IRS 2 and decreased docking of p85alpha to IRS 2 . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| The decreased activity of the insulin / IGF 1 signaling pathway is indicated by decrease of ( a ) IRS two pool levels ; ( b ) docking of p 85 alpha to IRS 2 ; ( c ) docking of p 85 alpha to p 110 alpha or p 110 beta , and ( d ) IRS 2 associated PI3K activity . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| IRS 2 and phosphotyrosine associated PI3K activity were increased 3 . 5 and 4 . 8 fold , respectively , by insulin in glycerol infused rats but only 1 . 6 and 2 . 3 fold in lipid infused rats . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| In the biopsies , insulin receptor kinase ( IRK ) activity , insulin receptor substrate ( IRS ) 1 associated phosphatidylinositol 3 kinase ( PI3K ) activity , Ser ( 473 ) and Thr ( 308 ) phosphorylation of protein kinase B ( PKB ) , and protein expression of IRS 1 , IRS 2 , phosphoinositol dependent kinase 1 ( PDK 1 ) , PKB , and GLUT 4 were determined . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| AT 2 receptor stimulation did not change insulin induced tyrosine phosphorylation of IRS 2 or its association with the p85alpha subunit of PI3K , but led to a significant reduction of insulin induced p85alpha phosphorylation . ^^^ Overexpression of a catalytically inactive dominant negative SHP 1 markedly attenuated the AT 2 receptor mediated inhibition of IRS 2 associated PI3K activity , Akt phosphorylation , and antiapoptotic effect induced by insulin . ^^^ Taken together , these results indicate that AT 2 receptor mediated activation of SHP 1 and the consequent inhibition IRS 2 associated PI3K activity contributed at least partly to the inhibition of Akt phosphorylation , thereby inducing apoptosis . . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Chronic treatment of insulin 100 nmol / L induced a significant reduction in the phosphorylation and protein expression of IR ? , IRS 1 and IRS 2 , which therefore resulted in a downregulation of association of PI3K with IRS . ^^^ In contrast , metformin in pharmacological concentration ( 1 10 mmol / L ) further inhibited tyrosine phosphorylation of IR ? , IRS 1 , IRS 2 and the interaction of PI3K with IRS . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Shb overexpression resulted also in the assembly and activation of a multiunit complex consisting of at least Shb , IRS 1 , IRS 2 , FAK , and PI3K . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| RINm5F cells overexpressing wild type GTK also exhibited reduced activation of IRS 2 , PI3K and AKT , whereas cells expressing a GTK mutant with lower kinase activity ( GTK ( Y394F ) ) exhibited insignificantly altered responses to insulin compared to the mock transfected cells . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Using an immunohistochemical technique to detect PI 3 , 4 , 5 triphosphate , the main product of PI3K activity , we further demonstrate that in the arcuate nucleus , insulin induced PI3K activity occurs preferentially within cells that contain IRS 2 . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| The MEK 1 mutant , which activates ERK , markedly down regulated expression of the insulin receptor ( IR ) and its major substrates , IRS 1 and IRS 2 , mRNA and protein , and in turn reduced tyrosine phosphorylation of IR as well as IRS 1 and IRS 2 and their associated phosphatidyl inositol 3 kinase ( PI3K ) activity . ^^^ The MKK 6 mutant , which activates p 38 , moderately inhibited IRS 1 and IRS 2 expressions and IRS 1 associated PI3K activity without exerting a significant effect on the IR . ^^^ Finally , the MKK 7 mutant , which activates JNK , reduced tyrosine phosphorylation of IRS 1 and IRS 2 and IRS associated PI3K activity without affecting expression of the IR , IRS 1 , or IRS 2 . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Desensitization was correlated to a reduction in insulin receptor substrate ( IRS ) 1 and IRS 2 protein levels , which was reversed by the PI3K inhibitor LY 294002 . ^^^ Contrarily , insulin induced IRS 2 down regulation occurred via a PI3K / mTOR pathway . ^^^ In summary , ( 1 ) PI3K mediates insulin induced reduction of IRS 1 by phosphorylating it while a PI3K / mTOR pathway controls insulin induced reduction of IRS 2 , ( 2 ) in L 6 cells , IRS 2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK , ( 3 ) the mechanism of IRS 1 / 2 down regulation is different in L 6 cells compared with 3T3 L 1 adipocytes . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| This was accompanied by reduced expression of IRS 2 and attenuated insulin stimulated recruitment of PI3K to IRS 1 and IRS 2 , yet insulin stimulated PKB activity and phosphorylation of eNOS at Ser 1177 were unaffected . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| We then identified an increase in JAK 2 , IRS 1 and IRS 2 tyrosine phosphorylation and in their association with p 85 , a subunit of PI3K . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| METHODS : We determined the expression and tyrosyl phosphorylation of the insulin receptor beta subunit ( IRbeta ) , IRS 1 and IRS 2 , the binding of phosphatidylinositol 3 kinase ( PI3K ) , and activation of the mitogen activated protein kinase ( MAPK ) pathway in the presence or absence of insulin stimulation in vivo during development and in the adult liver . ^^^ In contrast , there was a high level of IRS 2 expression and insulin stimulated tyrosyl phosphorylation as early as embryonic day 15 with robust PI3K binding and activation , which may enhance hepatocyte survival during the rapid growth phase of the liver . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Furthermore , PDGF stimulates these effects independent of insulin receptor substrate ( IRS ) 1 or IRS 2 tyrosine phosphorylation or docking to activated PI3K . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Insulin stimulated association of PI3K with IRS 1 and IRS 2 , and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation , while Grb 2 IRS association was unchanged . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Furthermore , progestin treatment prior to IGF 1 stimulation resulted in higher tyrosine phosphorylated IRS 2 levels , increased binding of IRS 2 to Grb 2 and the PI3K regulatory subunit p 85 , and correspondingly enhanced ERK and Akt activation , as compared with IGF 1 only conditions . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Analysis of genes encoding proteins that may activate the pathway upstream of Pi3k revealed variable fractions of tumors with EGFR amplification ( 31 % ) , PDGFRA amplification ( 8 % ) , and IRS 2 amplification ( 2 % ) . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Leptin treatment at this dose improved insulin stimulated insulin receptor and insulin receptor substrate 2 ( IRS 2 ) phosphorylation , IRS 2 associated PI3K activity , and Akt activity in liver . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway ( insulin ; A 23T , insulin like growth factor 1 receptor [ IGF 1R ] ; GAG1013GAA , plasma cell membrane glycoprotein 1 [ PC 1 ] ; K121Q , insulin receptor substrate [ IRS 1 ] ; G972R , insulin receptor substrate 2 [ IRS 2 ] ; G1057D and phosphatidylinositol 3 kinase p 85 alpha [ PI3K ] ; M326I ) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Presumably , IRS 2 or other PI3K activators account for the normal activation of aPKC in liver and PKB in adipocytes of IRS 1 knockout mice . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| This is the result of downregulation of the insulin receptor substrates , IRS 1 and IRS 2 , which become limiting for signal transmission from the insulin receptor to PI3K . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| In the present study , we examined the protein levels and phosphorylation state of insulin receptor ( IR ) , IRS 1 and IRS 2 , the association between IRSs and PI3K and SHP 2 , the insulin induced IRSs associated PI 3 kinase activities , and the phosphorylation status of AKT and atypical PKCzeta / lambda in the liver and the muscle of 6 month old Wistar rats treated with DHEA . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Although insulin receptor substrate 1 ( IRS 1 ) and IRS 2 , among other factors , activate PI3K , there is little information on the relative roles of IRS 1and IRS 2 during aPKC activation by insulin action in specific cell types . ^^^ We have also used these adipocytes to see if IRS 1 and IRS 2 are required for activation of Cbl , which is required for insulin stimulated glucose transport and has been found to function upstream of both PI3K / aPKC and Crk during thiazolidinedione action in 3T3 / L1 adipocytes [ Miura et al . ( 2003 ) Biochemistry 42 , 14335 ] . ^^^ Knockout of IRS 1 or IRS 2 also inhibited insulin induced increases in Cbl binding to the p 85 subunit of PI3K , which , along with IRS 1 / 2 , may be required for activation of PI3K , aPKC , and glucose transport during insulin action in 3T3 / L1 adipocytes . ^^^ These findings provide evidence that directly links both IRS 1 and IRS 2 to aPKC activation in immortalized brown adipocytes , and further suggest that IRS 1 and IRS 2 are required for the activation of Cbl / PI3K during insulin action in these cells . . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Acute insulin treatment stimulates glucose transport largely by mediating translocation of GLUT 4 to the plasma membrane , involving the activation of IRS 2 / PI3K , and the downstream targets Akt and protein kinase C zeta . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Because activation of PKB can require insulin receptor substrate proteins ( IRS 1 and IRS 2 ) and phosphatidylinositol 3 kinase ( PI3K ) , it is of interest to determine whether the activity of Foxo 1 is also regulated by heterotrimeric G protein coupled receptors ( GPCRs ) with IRS 1 or 2 , PI3K , or PKB signaling potential . ^^^ Indeed , studies of beta cells have demonstrated that activation of a GPCR for the blood glucose lowering hormone GLP 1 leads to major alterations of IRS 2 , PI3K , and PKB activity . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| We have also showed that insulin and leptin are able to activate PI3K through IRS 1 ( insulin receptor substrate 1 ) and IRS 2 respectively . ^^^ Furthermore , leptin or insulin pre treatment increased basal PI3K activity and IRS 1 or IRS 2 association with p 85 and abolished acute insulin or leptin effect , in addition to the down regulation of IRS 1 and IRS 2 . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| Biochemical analyses demonstrated that chronic Akt activation induces feedback inhibition of PI3K activity through both proteasome dependent degradation of insulin receptor substrate 1 ( IRS 1 ) and inhibition of transcription of IRS 1 as well as that of IRS 2 . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| In these cells , insulin induced tyrosine phosphorylation of IRS 1 / IRS 2 and recruitment of phosphoinositide 3 kinase ( PI3K ) to IRS 1 / IRS 2 were augmented by approximately 63 % . ^^^ Thus , stimulation of nAChRs up regulated expression of IRS 1 / IRS 2 via Ca ( 2+ ) dependent sequential activation of cPKC alpha and ERK , and enhanced insulin induced PI3K / Akt / GSK 3beta and ERK signaling pathways . . ^^^ |
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| Interacting proteins: O00329 and Q9Y4H2 |
Pubmed |
SVM Score :0.0 |
| The detection of mRNAs for insulin receptor ( IR ) A and IRB ; insulin receptor substrate ( IRS ) 1 and IRS 2 ; phosphoinositide 3 kinase ( PI3K ) catalytic subunits p110alpha , p110beta , PI3KC2alpha , and PI3KC2gamma ; phosphoinositide dependent protein kinase 1 ; protein kinase B ( PKB ) alpha , PKBbeta , and PKBgamma in the beta cell population suggests the presence of a functional insulin signaling cascade in human beta cells . ^^^ |
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