Blero D, De Smedt F, Pesesse X, Paternotte N, Moreau C, Payrastre B, Erneux C
Interdisciplinary Research Institute (IRIBHN), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, Brussels, 1070, Belgium.
Biochem Biophys Res Commun. 2001 Apr 6;282(3):839-43. doi: 10.1006/bbrc.2001.4639.
The lipid phosphatase SHIP2 (SH2 domain containing inositol 5-phosphatase 2) 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 anti-phosphotyrosine 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.
脂质磷酸酶SHIP2（含SH2结构域的肌醇5-磷酸酶2）最近被证明在体内是胰岛素信号传导和胰岛素敏感性的有效负调节因子。我们在此表明，SHIP2在过表达胰岛素受体的中国仓鼠卵巢细胞（CHO-IR细胞）中表达，并在胰岛素刺激后发生酪氨酸磷酸化。我们发现，在胰岛素刺激的细胞中，SHIP2被募集到抗磷酸酪氨酸免疫沉淀物中，这解释了Guilherme等人（《生物化学杂志》271卷，29533 - 29536页，1996年）报道的胰岛素敏感性或活性的明显增加。SHIP2的过表达导致胰岛素依赖性PIP3生成减少，以及Akt/PKB激活和MAPK刺激减弱。
