Drake P G, Balbis A, Wu J, Bergeron J J, Posner B I
Polypeptide Hormone Laboratory, McGill University, Montreal, Quebec, Canada H3A 2B2.
Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E266-74. doi: 10.1152/ajpendo.2000.279.2.E266.
Phosphatidylinositol 3-kinase (PI 3-kinase) plays an important role in a variety of hormone and growth factor-mediated intracellular signaling cascades and has been implicated in the regulation of a number of metabolic effects of insulin, including glucose transport and glycogen synthase activation. In the present study we have examined 1) the association of PI 3-kinase with the insulin receptor kinase (IRK) in rat liver and 2) the subcellular distribution of PI 3-kinase-IRK interaction. Insulin treatment promoted a rapid and pronounced recruitment of PI 3-kinase to IRKs located at the plasma membrane, whereas no increase in association with endosomal IRKs was observed. In contrast to IRS-1-associated PI 3-kinase activity, association of PI 3-kinase with the plasma membrane IRK did not augment the specific activity of the lipid kinase. With use of the selective PI 3-kinase inhibitor wortmannin, our data suggest that the cell surface IRK beta-subunit is not a substrate for the serine kinase activity of PI 3-kinase. The functional significance for the insulin-stimulated selective recruitment of PI 3-kinase to cell surface IRKs remains to be elucidated.
磷脂酰肌醇3激酶（PI 3激酶）在多种激素和生长因子介导的细胞内信号级联反应中发挥重要作用，并且与胰岛素的许多代谢效应的调节有关，包括葡萄糖转运和糖原合酶激活。在本研究中，我们检测了：1）大鼠肝脏中PI 3激酶与胰岛素受体激酶（IRK）的关联；2）PI 3激酶-IRK相互作用的亚细胞分布。胰岛素处理促使PI 3激酶迅速且显著地募集到位于质膜的IRK，而与内体IRK的关联未观察到增加。与IRS-1相关的PI 3激酶活性相反，PI 3激酶与质膜IRK的关联并未增强脂质激酶的比活性。使用选择性PI 3激酶抑制剂渥曼青霉素，我们的数据表明细胞表面IRKβ亚基不是PI 3激酶丝氨酸激酶活性的底物。胰岛素刺激的PI 3激酶向细胞表面IRK的选择性募集的功能意义仍有待阐明。
