Angiotensin ii-induced tyrosine phosphorylation stimulates
phospholipase c-g1 and cl- channels in mesangial cells.
Marrero, Mario B., Bernard Schieffer, Heping Ma, Kenneth E. Bernstein,
and Brian N. Ling.
Renal Division and Center for Cell and Molecular Signaling,
Departments of Medicine and Pathology, Emory University School of
Medicine and Veterans Affairs Medical Center, Atlanta, Georgia
APStracts 2:0447C, 1995.
Angiotensin II (AII)-induced, activation of phospholipase C (PLC) and
Ca2+-dependent Cl- channels is an important signal transduction
pathway for mesangial cell contraction and growth. While AII
receptors are traditionally thought to be G-protein coupled, recent
evidence suggests that they may also mediate protein tyrosine
phosphorylation. In cultured rat mesangial cells, 10-7 M AII
stimulated the tyrosine phosphorylation of PLC-[gamma]1, and
elevation of intracellular 1,4,5-IP3 and Ca2+ levels; peak response
occurred within 0.5 min. In cell-attached patches, AII stimulated the
activity of Ca2+-dependent, 3-4 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
AII-induced responses. We conclude that: 1) Stimulation of
inositolphosphate hydrolysis by PLC, release of IP3-dependent
intracellular Ca2+ stores, and activation of Ca2+-dependent Cl-
channels by AII is dependent on the tyrosine phosphorylation of PLC
-[gamma]1. 2) This AII-induced signal transduction cascade provides a
possible mechanism for both the contractile and growth-stimulating
effects of AII on glomerular mesangial cells.
Received 10 April 1995; accepted in final form 6 December 1995.
APS Manuscript Number C202-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95