Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-γ1 in vascular smooth muscle cells

Mario B Marrero, William G. Paxton, Jennifer L. Duff, Bradford C. Berk, Kenneth E. Bernstein

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203 Scopus citations

Abstract

The receptor for angiotensin II (Ang II) has recently been cloned; it is a receptor with seven transmembrane spanning domains that stimulates phosphoinositide hydrolysis upon ligand binding. The physiologic effects of Ang II are important in the regulation of vascular function. In this study, we examined the ability of Ang II to regulate the enzymatic activity of phospholipase C (PLC) in rat aortic vascular smooth muscle cells (VSMC). In cultured VSMC, PLC-γ1 and PLC-δ1 isozymes, but not PLC-β1, were identified by Western analysis. Ang II (10-7 M)-stimulated PLC-γ1 phosphotyrosine phosphorylation with a maximum increase of 4.5-fold at 0.5 min. This followed the same time course as the Ang II-stimulated increase in inositol 1,4,5- triphosphate (1,4,5-IP3) levels. 1,4,5-IP3 formation was inhibited 75% by the tyrosine kinase inhibitor genistein (120 μM). Several growth factor receptors, such as the platelet-derived growth factor (PDGF) receptor are themselves tyrosine kinases and have been shown to phosphorylate PLC-γ1 and increase intracellular Ca2+ concentrations. The time course for PLC-γ1 phosphorylation, IP3 formation, and Ca2+ mobilization by PDGF differed from Ang II in VSMC. The kinetics of the PDGF effects were slower in onset and more prolonged than those of Ang II. In summary, these findings show that Ang II stimulates VSMC phosphoinositide hydrolysis in association with tyrosine phosphorylation of PLC-γ1 and support the concept that Ang II- stimulated tyrosine phosphorylation is responsible for early signal transduction events.

Original languageEnglish (US)
Pages (from-to)10935-10939
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number14
StatePublished - Apr 8 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C., & Bernstein, K. E. (1994). Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-γ1 in vascular smooth muscle cells. Journal of Biological Chemistry, 269(14), 10935-10939.