Virbasius J V, Guilherme A, Czech M P
Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, USA.
J Biol Chem. 1996 Jun 7;271(23):13304-7. doi: 10.1074/jbc.271.23.13304.
Phosphatidylinositol (PI) 3-kinases catalyze the formation of 3'-phosphoinositides, which appear to promote cellular responses to growth factors and such membrane trafficking events as insulin-stimulated translocation of intracellular glucose transporters. We report here the cloning of a novel PI 3-kinase, p170, from cDNA of insulin-sensitive mouse 3T3-L1 adipocytes. Mouse p170 utilizes PI and to a limited extent PI 4-P as substrates, in contrast to the PI-specific yeast VPS34 homolog PtdIns 3-kinase and the p110 PI 3-kinases, which phosphorylate PI, PI 4-P, and PI 4,5-P2. Mouse p170 is also distinct from PtdIns 3-kinase or the p110 PI 3-kinases in exhibiting a 10-fold lower sensitivity to wortmannin. Unique structural elements of p170 include C-terminal sequences strikingly similar to the phosphoinositide-binding C2 domain of protein kinase C isoforms, synaptotagmins, and other proteins. These features of mouse p170 are shared with a recently cloned Drosophila PI 3-kinase, DmPI3K_68D. Together, these proteins define a new class of PI 3-kinase likely influenced by cellular regulators distinct from those acting upon p110- or VPS34-like PI 3-kinases.
磷脂酰肌醇（PI）3-激酶催化3'-磷酸肌醇的形成，这似乎能促进细胞对生长因子的反应以及诸如胰岛素刺激的细胞内葡萄糖转运体易位等膜运输事件。我们在此报告从胰岛素敏感的小鼠3T3-L1脂肪细胞的cDNA中克隆出一种新型PI 3-激酶p170。与PI特异性酵母VPS34同源物磷脂酰肌醇3-激酶和p110 PI 3-激酶不同，小鼠p170利用PI并在有限程度上利用PI 4-P作为底物，后者可使PI、PI 4-P和PI 4,5-P2磷酸化。小鼠p170对渥曼青霉素的敏感性也比磷脂酰肌醇3-激酶或p110 PI 3-激酶低10倍，这也使其与众不同。p170独特的结构元件包括与蛋白激酶C亚型、突触结合蛋白和其他蛋白质的磷酸肌醇结合C2结构域极为相似的C末端序列。小鼠p170的这些特征与最近克隆的果蝇PI 3-激酶DmPI3K_68D相同。这些蛋白质共同定义了一类新的PI 3-激酶，它们可能受不同于作用于p110或VPS34样PI 3-激酶的细胞调节因子的影响。
