Premium
p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K
Author(s) -
Sánchez-Margalet Víctor,
Najib Souad
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00887-x
Subject(s) - proto oncogene tyrosine protein kinase src , microbiology and biotechnology , insulin receptor substrate , insulin receptor , sh2 domain , biology , mitosis , irs1 , sh3 domain , phosphotyrosine binding domain , signal transduction , biochemistry , chemistry , insulin , endocrinology , insulin resistance
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.