| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.58473067 |
| Thus , in PC 12 cells , RET MEN2A associates with the PI3K regulatory subunit p 85 and promotes activation of Akt ( also referred to as protein kinase B ) in a PI3K dependent fashion ; in addition , RET MEN2A promotes MAPK activation . 0.58473067^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| Ligand stimulation of neuronal cells induced the assembly of a large protein complex containing c Ret , Grb 2 , and tyrosine phosphorylated forms of Shc , p 85 ( PI3K ) , the adaptor Gab 2 , and the protein tyrosine phosphatase SHP 2 . ^^^ These results indicate that upon ligand stimulation , at least two distinct protein complexes assemble on phosphorylated Tyr 1062 of c Ret via Shc , one leading to activation of the Ras / Erk pathway through recruitment of Grb2 / Sos and another to the PI3K / Akt pathway through recruitment of Grb2 / Gab2 followed by p 85 ( PI3K ) and SHP 2 . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| We now report that RET carrying a representative MEN2A mutation at Cys 634 ( termed RET MEN2A ) activates PI3K and its downstream effector , the serine / threonine kinase AKT / protein kinase B . ^^^ We provide evidence that mutation of Tyr 1062 abrogates the binding of the p 85 regulatory subunit of PI3K to RET MEN2A and the subsequent stimulation of the PI3K / AKT pathway . ^^^ Furthermore , infection of rat fibroblasts with a retrovirus expressing a dominant interfering form of PI3K suppresses RET MEN2A dependent transformation , whereas overexpression of AKT enhances the RET MEN2A oncogenic potential . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| Accordingly , we show that Ret MEN2B is more active than Ret MEN2A in associating with She and in causing constitutive activation of the Ras / mitogen activated protein kinase and PI3K / Akt cascades . ^^^ We conclude that the MEN2B mutation specifically potentiates the ability of Ret to autophosphorylate Y 1062 and consequently to couple to the Ras / mitogen activated protein kinase and the PI3K / Akt pathways . ^^^ Phosphorylated Y 1062 is part of a Ret multiple effector docking site that mediates recruitment of the Shc adapter and of phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| Using the neuroectodermic SK N MC cell line , we found that the Ret tyrosine kinase activity is essential for GDNF to induce phosphatidylinositol 3 kinase ( PI3K ) / Akt and ERK pathways as well as cell rescue . ^^^ Altogether , these findings underscore the importance of the Ret / PI3K / Akt pathway in GDNF induced neuroectodermic cell survival . . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| Activation of RET resulted in increased levels of phosphatidylinositol 3 kinase ( PI3K ) activity and Akt / PKB phosphorylation . ^^^ The data suggest that activation of RET in the ureteric bud epithelium signals through PI3K to control outgrowth and branching morphogenesis . . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| We identified serine 696 in RET as a putative phosphorylation site by protein kinase A and found that mutation of this serine almost completely inhibited lamellipodia formation by GDNF without affecting activation of the PI3K / AKT signaling pathway . ^^^ Mutation of tyrosine 1062 in RET , whose phosphorylation is crucial for activation of PI3K , also inhibited lamellipodia formation by GDNF . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| Overexpressed Rai resulted in the potentiation of the Ret dependent activation of phosphatidylinositol 3 kinase ( PI3K ) and Akt . ^^^ Phosphorylated and hypophosphorylated Rai proteins form a constitutive complex with the p 85 subunit of PI3K : upon Ret triggering , the Rai PI3K complex is recruited to the tyrosine phosphorylated Ret receptor through the binding of the Rai PTB domain to tyrosine 1062 of Ret . ^^^ We propose that Rai potentiates the MAPK and PI3K signaling pathways and regulates Ret dependent and independent survival signals . . ^^^ |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| RET can activate various signaling pathways such as RAS / extracellular signal regulated kinase ( ERK ) , phosphatidylinositol 3 kinase ( PI3K ) / AKT , p 38 mitogen activated protein kinase ( MAPK ) and c Jun N terminal kinase ( JNK ) pathways . ^^^ |
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| Interacting proteins: P07949 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: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07949 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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