Karenberg T A, Fenn A, Sachinidis A, Hoppe J
Department of Physiological Chemistry, Theodor-Boveri-Institute, University of Würzburg, Germany.
Exp Cell Res. 1994 Jul;213(1):266-74. doi: 10.1006/excr.1994.1198.
AKR-2B mouse fibroblasts express similar numbers of alpha- or beta-type PDGF receptors on their surface. Previous studies showed that PDGF-AA alone was unable to stimulate cell proliferation. Simultaneous addition together with insulin-like growth factor I (IGF-I), itself also inactive, led to a significant proliferation of the cells. In an effort to explain this synergism of the two growth factors we describe here the effects of the isoforms PDGF-AA or -BB and insulin-like growth factor I on three distinct signaling pathways, i.e., polyphosphoinositol turnover and [Ca2+]i increase, phosphatidylinositol-3 kinase, and mitogen-activated protein kinases. Whereas PDGF-BB effectively stimulated all three events, PDGF-AA failed to stimulate the phosphatidylinositol-3 kinase activity, but stimulated the mitogen-activated protein kinase to a maximum extent. In contrast IGF-I had no effect on mitogen-activated kinase but strongly stimulated phosphatidylinositol-3 kinase activity.
AKR-2B小鼠成纤维细胞在其表面表达数量相似的α型或β型血小板衍生生长因子（PDGF）受体。先前的研究表明，单独的PDGF-AA无法刺激细胞增殖。与本身也无活性的胰岛素样生长因子I（IGF-I）同时添加，会导致细胞显著增殖。为了解释这两种生长因子的协同作用，我们在此描述了PDGF-AA或-BB亚型以及胰岛素样生长因子I对三种不同信号通路的影响，即多磷酸肌醇代谢和细胞内钙离子浓度（[Ca2+]i）升高、磷脂酰肌醇-3激酶以及丝裂原活化蛋白激酶。虽然PDGF-BB能有效刺激所有这三种反应，但PDGF-AA未能刺激磷脂酰肌醇-3激酶活性，却能最大程度地刺激丝裂原活化蛋白激酶。相比之下，IGF-I对丝裂原活化激酶没有影响，但强烈刺激磷脂酰肌醇-3激酶活性。
