TY - JOUR
T1 - ANG II-induced tyrosine phosphorylation stimulates phospholipase C-γ1 and Cl- channels in mesangial cells
AU - Marrero, Mario B.
AU - Schieffer, Bernhard
AU - Ma, Heping
AU - Bernstein, Kenneth E.
AU - Ling, Brian N.
PY - 1996/6
Y1 - 1996/6
N2 - Angiotensin II (ANG II)-induced, activation of phospholipase C (PLC) and Ca2+-dependent Cl- channels is an important signal transduction pathway for mesangial cell contraction and growth. Although ANG II 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 ANG II stimulated the tyrosine phosphorylation of PLC-γ1 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 Ca2+-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 Ca2+-dependent Cl- channels by ANG II are dependent on the tyrosine phosphorylation of PLC-γ1. 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.
AB - Angiotensin II (ANG II)-induced, activation of phospholipase C (PLC) and Ca2+-dependent Cl- channels is an important signal transduction pathway for mesangial cell contraction and growth. Although ANG II 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 ANG II stimulated the tyrosine phosphorylation of PLC-γ1 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 Ca2+-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 Ca2+-dependent Cl- channels by ANG II are dependent on the tyrosine phosphorylation of PLC-γ1. 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.
KW - angiotensin II
KW - genistein
KW - herbimycin A
KW - inositol 1,4,5-trisphosphate
KW - intracellular calcium
KW - thapsigargin
KW - tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=0029747150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029747150&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.1996.270.6.c1834
DO - 10.1152/ajpcell.1996.270.6.c1834
M3 - Article
C2 - 8764169
AN - SCOPUS:0029747150
SN - 0363-6143
VL - 270
SP - C1834-C1842
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 6 39-6
ER -