Schieffer B, Paxton W G, Chai Q, Marrero M B, Bernstein K E
Department of Pathology Center for Molecular and Cellular Signaling, Emory University, Atlanta, Georgia 30322, USA.
J Biol Chem. 1996 Apr 26;271(17):10329-33. doi: 10.1074/jbc.271.17.10329.
Angiotensin II is the major effector peptide of the renin-angiotensin system, and it exerts its physiologic functions via a G protein-coupled cell surface receptor called AT1. We found that in rat aortic smooth muscle cells, angiotensin II stimulated the formation of Ras-GTP, Ras-Raf-1 complex formation, and the tyrosine phosphorylation of two important Ras GTPase-activating proteins (GAPs), p120 Ras-GAP and p190 Rho-GAP. Electroporation of anti-pp60c-src antibody into cultured, adherent smooth muscle cells blocked the angiotensin II stimulation of Ras-GAP and Rho-GAP tyrosine phosphorylation. In contrast electroporation of antibodies against c-Yes or c-Fyn had no effect. Anti-pp60c-src antibody also blocked angiotensin II-stimulated Ras activation and Ras-Raf-1 complex formation. These data strongly suggest that a G protein-coupled receptor such as the AT1 receptor can activate the Ras protein cascade via the tyrosine kinase pp60c-src.
血管紧张素II是肾素-血管紧张素系统的主要效应肽，它通过一种名为AT1的G蛋白偶联细胞表面受体发挥其生理功能。我们发现，在大鼠主动脉平滑肌细胞中，血管紧张素II刺激Ras-GTP的形成、Ras-Raf-1复合物的形成，以及两种重要的Ras GTP酶激活蛋白（GAPs）——p120 Ras-GAP和p190 Rho-GAP的酪氨酸磷酸化。将抗pp60c-src抗体电穿孔导入培养的贴壁平滑肌细胞中，可阻断血管紧张素II对Ras-GAP和Rho-GAP酪氨酸磷酸化的刺激作用。相比之下，针对c-Yes或c-Fyn的抗体电穿孔则没有效果。抗pp60c-src抗体还可阻断血管紧张素II刺激的Ras激活和Ras-Raf-1复合物的形成。这些数据强烈表明，诸如AT1受体这样的G蛋白偶联受体可通过酪氨酸激酶pp60c-src激活Ras蛋白级联反应。
