Phosphorylation of p130(Cas) by angiotensin II is dependent on c-Src, intracellular Ca2+, and protein kinase C

Peter P. Sayeski, M. Showkat Ali, Joyce B. Harp, Mario B. Marrero, Kenneth E. Bernstein

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

p130(Cas) is a signaling molecule that was initially found to be tyrosine-phosphorylated in v-Crk and v-Src transformed cells. We characterized the regulation of p130(cas) tyrosine phosphorylation in vascular smooth muscle cells by angiotensin II (Ang II). This ligand induced a transient increase in p130(Cas) tyrosine phosphorylation, which was sensitive to the actin polymerization inhibitor cytochalasin D and to the intracellular Ca2+ chelator BAPTA-AM but not the Ca2+ channel blocker verapamil. The Ang II-induced tyrosine phosphorylation of p130(Cas) was also dependent on an active Src family tyrosine kinase, since it could be blocked by the Src kinase inhibitors geldanamycin and PP1. Ang II treatment resulted in the ability of p130(Cas) to bind at least 11 different phosphate- containing proteins. Analysis of these proteins revealed that protein kinase Cα and the cell adhesion signaling molecule pp120 formed temporal associations with p130(Cas) in response to Ang II. c-Src was found to associate with p130(Cas) in a manner that was independent of Ang II treatment. Inhibition of protein kinase C by either calphostin C or phorbol 12-myristate 13-acetate downregulation inhibited the Ang II-induced tyrosine phosphorylation of p130(Cas). These results are the first to demonstrate that the tyrosine phosphorylation of p130(Cas) by Ang II is transduced by the Src, intracellular Ca2+, protein kinase C signaling pathway.

Original languageEnglish (US)
Pages (from-to)1279-1288
Number of pages10
JournalCirculation research
Volume82
Issue number12
DOIs
StatePublished - Jun 29 1998

Keywords

  • Angiotensin II
  • P130(Cas)
  • Tyrosine phosphorylation
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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