Electroporation of pp60c-src antibodies inhibits the angiotensin II activation of phospholipase C-γ1 in rat aortic smooth muscle cells

Mario B. Marrero, Bernhard Schieffer, William G. Paxton, Elisabeth Schieffer, Kenneth E. Bernstein

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164 Scopus citations

Abstract

Our previous study has shown that angiotensin II induces the rapid tyrosine phosphorylation and activation of phospholipase C-γ1 in cultured rat aortic smooth muscle (RASM) cells (Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C., and Bernstein, K. E. (1994) J. Biol. Chem. 269, 10935-10939). This signaling pathway is initiated by ligand binding to the AT1 receptor, a cell surface G protein-coupled receptor. Antibodies to pp60c-Src were introduced into RASM cells by electroporation. Angiotensin II-stimulated tyrosine phosphorylation of phospholipase C-γ1 was eliminated by the anti-pp60c-src antibodies but not by anti-mouse IgG or bovine serum albumin. Angiotensin II also induced the rapid tyrosine phosphorylation of pp120, a known pp60c-src kinase substrate, and this phosphorylation was also specifically inhibited by anti-pp60c-arc antibodies. Electroporation of RASM cells with anti-pp60c-src antibodies had no effect on platelet-derived growth factor-stimulated tyrosine phosphorylation of PLC-γ1. Anti-pp60c-src also reduced the angiotensin II-stimulated inositol 1,4,5-trisphosphate production by 78%, while it had no effect on the platelet-derived growth factor-stimulated inositol 1,4,5-trisphosphate production. These data provide the first evidence for a direct involvement of pp60c-src kinase in angiotensin II-mediated PLC-γ1 phosphorylation and activation. Furthermore, it also describes a pathway in which a seven-transmembrane receptor can stimulate an intracellular tyrosine kinase.

Original languageEnglish (US)
Pages (from-to)15734-15738
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number26
DOIs
StatePublished - Jun 30 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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