p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K

FEBS Letters

Najib, Souad¹  Sánchez-Margalet, Víctor¹ 

[1] Department of Medical Biochemistry and Molecular Biology, School of Medicine, University of Seville and Investigation Unit, University Hospital Virgen Macarena, Av. Sanchez Pizjuan, 4, 41009 Seville, Spain

关键词: Insulin receptor;    Insulin receptor substrate;    Src associated in mitosis 68;    Src homology 2 domain;    p85 phosphatidylinositol-3-kinase;    Sam;    Src associated in mitosis;    PI3K;    phosphatidylinositol-3-kinase;    IR;    insulin receptor;    IRS-1;    insulin receptor substrate-1;    SH;    Src homology;    GST;    glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(99)00887-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling. We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis 68 may be part of the signaling complexes of insulin receptor along with p85. In vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.

【 授权许可】

Unknown