The SH2 domain containing inositol 5-phosphatase SHIP2 controls phosphatidylinositol 3,4,5-trisphosphate levels in CHO-IR cells stimulated by insulin

The lipid phosphatase SHIP2 ((SH) under bar2 domain containing (i) under bar nositol 5-(p) under bar hosphatase (2) under bar) has recently been shown to be a potent negative regulator of insulin signaling and insulin sensitivity in vivo, We show here that SHIP2 is expressed in Chinese hamster ovary cells overexpressing the insulin receptor (CHO-IR cells) and tyrosine phosphorylated upon insulin stimulation. We show that SHIP2, which is recruited in antiphosphotyrosine immunoprecipitates in insulin-stimulated cells, accounts for the insulin sensitivity or apparent increase in activity reported by Guilherme et al, (J. Biol. Chem, 271, 29533-29536, 1996), Overexpression of SHIP2 led to a decrease of the insulin-dependent PIP3 production as well as Akt/PKB activation and MAPK stimulation. (C) 2001 Academic Press.