Marrero M B, Schieffer B, Ma H, Bernstein K E, Ling B N
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Am J Physiol. 1996 Jun;270(6 Pt 1):C1834-42. doi: 10.1152/ajpcell.1996.270.6.C1834.
Angiotensin II (ANG II)-induced, activation of phospholipase C (PLC) and Ca(2+)-dependent Cl-channels is an important signal transduction pathway for mesangial cell contraction and growth. Although ANG II receptors are traditionally though to be G protein coupled, recent evidence suggests that they may also mediate protein tyrosine phosphorylation. In cultured rat mesangial cells, 10(-7) MANG II stimulated the tyrosine phosphorylation of PLC-gamma 1 and elevation of intracellular inositol 1,4,5-trisphosphate (IP3) and Ca2+ levels; peak response occurred within 0.5 min. In cell-attached patches, ANG II stimulated the activity of Ca(2+)-dependent, 3- to 4-pS Cl-channels (number of channels x open probability) from 0.063 +/- 0.022 to 0.77 +/- 0.20. Tyrosine kinase inhibition with genistein or herbimycin A blocked all four ANG II-induced responses. We conclude the following. 1) Stimulation of inositol phosphate hydrolysis by PLC, release of IP3-dependent intracellular Ca2+ stores, and activation of Ca(2+)-dependent C1-channels by ANG II are dependent on the tyrosine phosphorylation of PLC-gamma 1.2) This ANG II-induced signal transduction cascade provides a possible mechanism for both the contractile and growth-stimulating effects of ANG II on glomerular mesangial cells.
血管紧张素II（ANG II）诱导的磷脂酶C（PLC）激活和Ca（2+）依赖性Cl通道是系膜细胞收缩和生长的重要信号转导途径。尽管传统上认为ANG II受体是G蛋白偶联的，但最近的证据表明它们也可能介导蛋白酪氨酸磷酸化。在培养的大鼠系膜细胞中，10（-7）MANG II刺激PLC-γ1的酪氨酸磷酸化以及细胞内肌醇1,4,5-三磷酸（IP3）和Ca2+水平的升高；峰值反应在0.5分钟内出现。在细胞贴附片膜中，ANG II将Ca（2+）依赖性、3至4 pS的Cl通道活性（通道数量×开放概率）从0.063±0.022提高到0.77±0.20。用金雀异黄素或赫曲霉素A抑制酪氨酸激酶可阻断所有四种ANG II诱导的反应。我们得出以下结论。1）ANG II通过PLC刺激肌醇磷酸水解、释放IP3依赖性细胞内Ca2+储存以及激活Ca（2+）依赖性Cl通道均依赖于PLC-γ1的酪氨酸磷酸化。2）这种ANG II诱导的信号转导级联为ANG II对肾小球系膜细胞的收缩和生长刺激作用提供了一种可能的机制。
