Molecular interactions of SHP1 and SHP2 in IL-3-signalling

阅读量：

作者：

展开

摘要：

SHP1 and SHP2 tyrosine phosphatases have both been implicated in signalling pathways downstream of the interleukin-3 (IL-3) receptor. We have investigated the co-association of SHP1 and SHP2 with tyrosine-phosphorylated proteins in IL-3-dependent BaF/3 cells. We demonstrate that both SHP1 and SHP2 associate with Aic2A (β chain of the IL-3 receptor), Gab2 and the paired inhibitory receptor B (PIR-B). The individual SH2 domains of SHP2 can independently bind Gab2, potentially important for the adapter function of SHP2. Association of both phosphatases with Aic2A and Gab2 increases upon IL-3 treatment. Recruitment of SHP1 to PIR-B also increases in response to IL-3, suggesting a functional link between inhibitory and cytokine receptor signalling. Aic2A is a rapid target for dephosphorylation following IL-3 stimulation and substrate-trapping versions of both phosphatases identify Aic2A and Gab2 as substrates for SHP1 and SHP2. These studies suggest that SH2–domain interactions are important for targetting these phosphatases to their substrates.

展开

关键词：

SH Src homology Src homology SHP SH2 protein tyrosine phosphatase SH2 protein tyrosine phosphatase PI3K phosphoinositide-3-kinase phosphoinositide-3-kinase GST glutathione S-transferase glutathione S-transferase IP immunoprecipitation immunoprecipitation