Hooshmand-Rad R, Hájková L, Klint P, Karlsson R, Vanhaesebroeck B, Claesson-Welsh L, Heldin C H
Ludwig Institute for Cancer Research, BMC, Box 595, S-751 24 Uppsala, Sweden.
J Cell Sci. 2000 Jan;113 Pt 2:207-14. doi: 10.1242/jcs.113.2.207.
Phosphoinositide 3'-kinases constitute a family of lipid kinases implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Phosphoinositide 3'-kinases that bind to the platelet-derived growth factor receptor are composed of two subunits: the p85 subunit acts as an adapter and couples the catalytic p110 subunit to the activated receptor. There are different isoforms of p85 as well as of p110, the individual roles of which have been elusive. Using microinjection of inhibitory antibodies specific for either p110(alpha) or p110(beta) we have investigated the involvement of the two p110 isoforms in platelet-derived growth factor- and insulin-induced actin reorganization in porcine aortic endothelial cells. We have found that antibodies against p110(alpha), but not antibodies against p110(beta), inhibit platelet-derived growth factor-stimulated actin reorganization, whereas the reverse is true for inhibition of insulin-induced actin reorganization. These data indicate that the two phosphoinositide 3'-kinase isoforms have distinct roles in signal transduction pathways induced by platelet-derived growth factor and insulin.
磷酸肌醇3'-激酶构成了一类脂质激酶家族，参与通过酪氨酸激酶受体和异源三聚体G蛋白偶联受体的信号转导。与血小板衍生生长因子受体结合的磷酸肌醇3'-激酶由两个亚基组成：p85亚基作为衔接蛋白，将催化性p110亚基与活化的受体偶联。p85以及p110存在不同的同工型，它们各自的作用一直难以捉摸。通过显微注射对p110α或p110β特异的抑制性抗体，我们研究了这两种p110同工型在血小板衍生生长因子和胰岛素诱导的猪主动脉内皮细胞肌动蛋白重排中的作用。我们发现，抗p110α抗体而非抗p110β抗体抑制血小板衍生生长因子刺激的肌动蛋白重排，而抑制胰岛素诱导的肌动蛋白重排则情况相反。这些数据表明，两种磷酸肌醇3'-激酶同工型在血小板衍生生长因子和胰岛素诱导的信号转导途径中具有不同的作用。
