| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.76246988 |
| Furthermore , phosphorylated Gab 1 binds and activates phosphatidylinositol 3 kinase ( PI3K ) in response to osmotic shock . 0.76246988^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.91753756 |
| Immunoprecipitation and pull down experiments revealed that regulatory subunit of PI3K , p 85 , was rapidly associated with tyrosine phosphorylated Gab 1 via its n and c terminal SH 2 domains . 0.91753756^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| We have examined the ability of epidermal growth factor ( EGF ) stimulated ERK activation to regulate Grb 2 associated binder 1 ( Gab 1 ) / phosphatidylinositol 3 kinase ( PI3K ) interactions . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| From these data , we derived a consensus sequence which predicts high affinity binding to PtdIns ( 3 , 4 ) P 2 and / or PtdIns ( 3 , 4 , 5 ) P 3 , and we have identified several new PH domain containing proteins that bind PI3K products , including Gab 1 , Dos , myosinX , and Sbf 1 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Although the mutated receptor had lost its ability to recruit and / or activate known signaling molecules , such as GRB 2 , SHC , GAB 1 , and PI3K , by using a sensitive association kinase assay we found that the mutated receptor can still associate and phosphorylate a approximately 250 kDa protein . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| The Gab 1 docking protein has been shown to regulate phosphatidylinositol 3 kinase PI3K activity and potentiate nerve growth factor ( NGF ) induced survival in PC 12 cells . ^^^ Finally , we found that HA Gab 1 induced neuritogenesis was completely suppressed by pharmacological inhibition of mitogen activated protein kinase kinase ( MEK ) activity and 50 % suppressed by inhibition of PI3K activity . ^^^ In contrast , HA Gab 1 stimulated cell survival was efficiently suppressed only by inhibition of both PI3K and MEK activities . ^^^ These results indicate that Gab 1 is capable of mediating differentiation , DNA synthesis , and cell survival and uses both PI3K and MEK signaling pathways to achieve its effects . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| In this study , we prepared Gab 1 mutants lacking the SHP 2 binding site ( Gab1Y627F ) , the phosphatidylinositol 3 kinase ( PI3K ) binding sites ( Gab1DeltaPI3K ) , and the PH domain ( Gab1DeltaPH ) . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| The docking proteins that the BCR uses to recruit PI3K include CD 19 , Cbl , Gab 1 , and perhaps Gab 2 . ^^^ We have shown that Gab 1 colocalizes PI3K with SH 2 domain containing inositol phosphatase ( SHIP ) and SHP 2 , two enzymes that regulate PI3K dependent signaling . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| These findings support a model where PI3K activity is dependent on its recruitment into TPO induced multiphosphoprotein complexes , implicate the existence of a scaffolding protein in primary MKs distinct from the known Gab and IRS proteins , and suggest that , in contrast to erythroid progenitor cells that employ Gab 1 in PI3K signaling complexes , utilization of an alternate member of the Gab / IRS family could be responsible for specificity in TPO signaling . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| In addition , we have observed that the docking protein Gab 1 , which is involved in PI3K activation during EGF stimulation , is also implicated in this pathway downstream of PI3K . ^^^ Indeed , the association of Gab 1 with SHP 2 was blocked by PI3K inhibitors , and expression of Gab 1 mutant deficient for binding to SHP 2 was found to inhibit Ras stimulation without interfering with PI3K activation . ^^^ These results show that , in addition to Shc and Grb 2 , a PI3K dependent pathway involving Gab 1 and SHP 2 is essential for Ras activation under EGF stimulation . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Both the tyrosine phosphatase SHP 2 and the multisubstrate docking molecule Gab 1 , which are potential links between IL 6 and the MAPK / PI3K pathways , were constitutively associated with the active EGF receptor . ^^^ On IL 6 stimulation , SHP 2 and Gab 1 were recruited to the gp 130 subunit of the IL 6 receptor and tyrosine phosphorylated , allowing downstream signaling to the MAPK and PI3K pathways . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| This allows phosphatidylinositol 3 kinase ( PI3K ) and the SHP 2 tyrosine phosphatase to bind to Gab 1 . ^^^ In this report , we tested the hypothesis that Gab 1 acts as an amplifier of PI3K and SHP 2 dependent signaling in B lymphocytes . ^^^ By overexpressing Gab 1 in the WEHI 231 B cell line , we found that Gab 1 can potentiate BCR induced phosphorylation of Akt , a PI3K dependent response . ^^^ Moreover , using confocal microscopy , we show that BCR ligation can induce the translocation of Gab 1 from the cytosol to the plasma membrane and that this requires the Gab 1 PH domain as well as PI3K activity . ^^^ These findings are consistent with a model in which the binding of the Gab 1 PH domain to PI3K derived lipids brings Gab 1 to the plasma membrane , where it can be tyrosine phosphorylated and then act as an amplifier of BCR signaling . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Based on our previous observations that active ERK associates with and phosphorylates Gab 1 in response to HGF , and the prediction that the ERK phosphorylation site is adjacent to one of the phosphatidylinositol 3 kinase ( PI3K ) SH 2 binding motifs , we examined the possibility that ERK phosphorylation can regulate the Gab1 / PI3K association . ^^^ These results suggest that activated ERK can phosphorylate Gab 1 in response to HGF stimulation and thereby potentiate the Gab1 / PI3K association and subsequent PI3K activation . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| In these cells , PI3K was constitutively associated with the molecular adapters Grb 2 and Gab 1 , and with the phosphatases SHP 2 and SHIP . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| The Src homology 2 ( SH 2 ) domain of the phosphatidylinositol 3 kinase ( PI3K ) regulatory subunit binds Gab 1 in a phosphorylation independent manner . ^^^ Moreover , the regulatory subunit of PI3K can mediate the association of Gab 1 and receptor protein tyrosine kinases including the insulin , EGF , and NGF receptors , all of which phosphorylate Gab 1 . ^^^ Thus , it appears that the PI3K regulatory subunit acts as an adaptor protein via a phosphotyrosyl independent SH 2 interaction , allowing Gab 1 to serve as a substrate for several tyrosine kinases . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| PymT mimics activated receptor tyrosine kinases by forming a ShcA Grb 2 Gab1 complex , thus inducing Gab 1 tyrosine phosphorylation , which itself is associated with PI3K . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation stimulates PI3K and PLCgamma 1 enzymatic activity , and on ShcA creates binding sites for Grb 2 with its associated Sos 1 and Gab 1 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Indeed , both membrane redistribution and phosphorylation of Gab 1 were reduced in the presence of PI3K inhibitors or dominant negative p110beta . ^^^ Downstream of Gab 1 , the tyrosine phosphatase SHP 2 was found to mediate Ras activation in response to LPA and to be recruited through PI3K and Gab 1 , because transfection of Gab 1 mutant deficient for SHP 2 binding inhibited Ras activation without interfering with PI3K activation . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Shp 2 mutant fibroblasts exhibit increased association of the p 85 subunit of PI3K with the scaffolding adapter Gab 1 compared to that for wild type ( WT ) fibroblasts or Shp 2 mutant cells reconstituted with WT Shp 2 . ^^^ Gab 1 associated PI3K activity is increased and PI3K dependent downstream signals are enhanced in Shp 2 mutant cells following EGF stimulation . ^^^ Our results suggest that , in addition to its role as a positive component of the Ras Erk pathway , Shp 2 negatively regulates EGF dependent PI3K activation by dephosphorylating Gab 1 p85 binding sites , thereby terminating a previously proposed Gab 1 PI3K positive feedback loop . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Consistent with the ability of Grb 2 to recruit SOS and Gab 1 , the Ras / MAPK and PI3K pathways are activated by Sf Stk , and both of these pathways are required for gp 55 mediated erythroblast proliferation . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| However , the NS5A Gab 1 association , which appeared indirect , was not mediated by direct NS5A Grb 2 interaction but was likely dependent on direct NS5A interaction with the p 85 subunit of phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Gab 1 then recruits molecules such as SHP 2 , phosphatidylinositol 3 kinase ( PI3K ) , and Shc . ^^^ Cell viability assays reveal that Gab 1 has a dual role in cell survival : a positive one through its interaction with PI3K and a negative one through its interaction with SHP 2 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitations showed that ErbB 3 and Grb 2 associated binder ( Gab ) 1 were phosphorylated and associated with PI3K activity after heregulin treatment and that Gab 1 and Gab 2 , but not ErbB 3 , were phosphorylated and associated with PI3K activity after EGF treatment . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Tumors exhibited increased association of Egfr with clathrin heavy chain ( CHC ) , Gab 1 , and p85alpha , the regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and tumors also overexpressed c Src , PDK 1 , and Akt . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| We previously reported that tyrosine 1062 in RET receptor tyrosine kinase activated by glial cell line derived neurotrophic factor ( GDNF ) represents a binding site for the Shc Grb 2 Gab1 complex , and that the p 85 subunit of phosphatidylinositol 3 kinase ( PI3K ) and SHP 2 tyrosine phosphatase is associated with Gab 1 in GDNF treated cells . ^^^ In the present study , we further analyzed the physiological roles of Gab 1 downstream of RET , using Gab 1 mutants that lack the binding sites for PI3K ( Gab 1 PI3K m ) or SHP 2 ( Gab 1 SHP2 m ) . ^^^ Expression of Gab 1 PI3K m in SK N MC human primitive neuroectodermal tumor cells expressing wild type RET markedly impaired Akt phosphorylation , Rac 1 activation , and lamellipodia formation that were induced by GDNF whereas expression of Gab 1 SHP2 m partially impaired Erk activation . ^^^ Furthermore , expression of Gab 1 PI3K m , but not Gab 1 SHP2 m , in TT human medullary thyroid carcinoma cells expressing RET with a multiple endocrine neoplasia 2A mutation enhanced cytochrome c release , and apoptosis induced by etoposide , suggesting that PI3K is involved in survival of TT cells via a mitochondrial pathway . ^^^ These findings demonstrated that coupling of Gab 1 to PI3K is important for biological responses in RET expressing cells . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| SHP 2 was recently found to down regulate PI3K activation by dephosphorylating Gab 1 but the mechanisms explaining the positive role of the Gab1 / SHP2 pathway in EGF induced Ras activation remain ill defined . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of Gab 1 by flow was functionally important , because flow stimulated the association of Gab 1 with the PI3K subunit p 85 in a time dependent manner . ^^^ These data demonstrate a critical role of Gab 1 in flow stimulated PI3K / Akt / eNOS signal pathway in endothelial cells . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Recent evidence indicates that the adapter molecule Gab 1 , together with the protein tyrosine phosphatase Shp 2 , is critically involved in regulating the strength and duration of phosphatidylinositol 3 kinase ( PI3K ) and Akt activation upon EGF stimulation in fibroblasts . ^^^ Our results show that stimulation of VSMCs with EGF as well as Ang 2 leads to a rapid tyrosine phosphorylation of Gab 1 and its association with the p 85 subunit of PI3K . ^^^ We therefore propose that RV blocks Akt activation in Ang 2 and EGF stimulated VSMCs by activating Shp 2 , thus preventing interaction between Gab 1 and PI3K that is necessary for further signal transduction . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| The effector pathway from the EGFR to PI3K in these nontransformed cells included the adaptor Grb 2 , the docking protein Gab 1 , and the phosphatase Shp 2 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| HGF stimulated Gab 1 association with c Met , Grb 2 , SHP 2 , PI3K , Shc , Crk isoforms and CrkL , but not with PLCgamma 1 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| These findings suggest that nuclear translocation of PIPS is involved in NGF mediated neuronal survival via TrkA , PI3K , and Gab 1 signaling pathway . . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Reduced phosphatase activity of SHP 2 in LEOPARD syndrome : consequences for PI3K binding on Gab 1 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we explore in silico and validate in vivo the role of GAB 1 in the control of mitogenic ( Ras / MAPK ) and survival ( phosphatidylinositol 3 kinase ( PI3K ) / Akt ) signaling stimulated by epidermal growth factor ( EGF ) . ^^^ We show that the temporal dynamics of GAB 1 tyrosine phosphorylation is significantly controlled by positive GAB 1 PI3K feedback and negative MAPK GAB 1 feedback . ^^^ Our experimental and computational results demonstrate that the essential function of GAB 1 is to enhance PI3K / Akt activation and extend the duration of Ras / MAPK signaling . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| We could detect the PI3K regulatory subunit p 85 in immunoprecipitates of endogenous Gab 1 , and vice versa , and measure a Gab 1 associated lipid kinase activity upon VEGF stimulation . ^^^ Furthermore , transfection of the Gab 1 YF3 mutant lacking all p 85 binding sites strongly repressed PI3K activation measured in vitro . ^^^ Furthermore , adenoviral expression of Gab 1 YF3 suppressed both Akt phosphorylation and recovery of wounded human umbilical vein endothelial cell monolayers , a VEGF dependent process involving cell migration and proliferation under PI3K control . ^^^ Transfection of other Gab 1 mutants , lacking Grb 2 binding sites or the pleckstrin homology ( PH ) domain , also prevented Akt activation , further demonstrating Gab 1 involvement in PI3K activation . ^^^ Importantly , Gab 1 mobilization was impaired by ( 1 ) PI3K inhibitors , ( 2 ) deletion of Gab 1 PH domain , ( 3 ) PTEN ( phosphatase and tensin homolog deleted on chromosome 10 ) overexpression to repress PtdIns ( 3 , 4 , 5 ) P 3 production , and ( 4 ) overexpression of a competitor PH domain for PtdIns ( 3 , 4 , 5 ) P 3 binding , which altogether demonstrated that PI3K is also an upstream regulator of Gab 1 . ^^^ |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|