| Interacting proteins: P07949 and Q06124 |
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 Q06124 |
Pubmed |
SVM Score :0.0 |
| Therefore , we investigated the impact of the tyrosine phosphatases SHP 1 and SHP 2 on the intrinsic tyrosine kinase activity and oncogenic potency of Ret with a 9 bp duplication in the cysteine rich domain ( codons 634 636 ) , which was described in a patient with MEN type 2A recently . ^^^ SHP 1 and SHP 2 were stably overexpressed in NIH3T3 fibroblasts together with Ret 9bp . ^^^ Coexpression of SHP 1 with Ret 9bp reduced the autophosphorylation of Ret 9bp by 19 + / 7 % ( P = 0 . 01 , n = 4 ) , whereas no effect was seen with SHP 2 . ^^^ Furthermore , Ret 9bp could be coimmunoprecipitated with SHP 1 but not with SHP 2 antibodies . ^^^ |
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| Interacting proteins: P07949 and Q06124 |
Pubmed |
SVM Score :0.0 |
| The tyrosine phosphatase Shp 2 mediates intracellular signaling initiated by Ret mutants . ^^^ Here we investigated the involvement of the Shp 2 tyrosine phosphatase in determining the downstream signaling pathways initiated by the Ret oncogene , carrying either the cysteine 634 to tyrosine or the methionine 918 to threonine substitutions . ^^^ The results indicate that Shp 2 is a downstream mediator of the mutated receptors RetC634Y and RetM918T , thus suggesting that it may act as a limiting factor in Ret associated endocrine tumors , in the neoplastic syndromes multiple endocrine neoplasia types 2A and 2B . . ^^^ |
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| Interacting proteins: P07949 and Q06124 |
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 ) . ^^^ |
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