ANG II-induced tyrosine phosphorylation stimulates phospholipase C-γ1 and Cl- channels in mesangial cells

Mario B. Marrero, Bernhard Schieffer, Heping Ma, Kenneth E. Bernstein, Brian N. Ling

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)C1834-C1842
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number6 39-6
Publication statusPublished - Jun 1 1996

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Keywords

  • angiotensin II
  • genistein
  • herbimycin A
  • inositol 1,4,5-trisphosphate
  • intracellular calcium
  • thapsigargin
  • tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Marrero, M. B., Schieffer, B., Ma, H., Bernstein, K. E., & Ling, B. N. (1996). ANG II-induced tyrosine phosphorylation stimulates phospholipase C-γ1 and Cl- channels in mesangial cells. American Journal of Physiology - Cell Physiology, 270(6 39-6), C1834-C1842.