Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells

M. Showkat Ali, Bernhard Schieffer, Patrick Delafontaine, Kenneth E. Bernstein, Brian N. Ling, Mario B Marrero

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Angiotensin II (Ang II) and insulin-like growth factor I (IGF I) stimulate intracellular signaling events through binding to their respective G-protein-coupled and growth factor receptors. In rat aortic vascular smooth muscle cells, IGF I (20 ng/ml) induced a sustained (>30 min) increase in the tyrosine phosphorylation of both Src-homology 2 domain-docking insulin receptor substrate 1 (IRS-1) and Src-homology 2-binding tyrosine phosphatase 1D (PTP-1D). In addition, IGF I stimulated PTP-1D phosphatase activity. Ang II (10-7 M) also increased the tyrosine phosphorylation of IRS-1 (4-fold), PTP-1D (5-fold), and PTP-1D activity (3-4-fold), but with a more transient time coarse. Ang II also induced PTP-1D-IRS-1 complex formation. These Ang II-induced events were not affected by preincubation with an anti-IGF I antibody, suggesting that Ang II's actions were not mediated via the autocrine secretion of IGF I. Anti-PTP-1D antibody electroporation attenuated Ang II-induced PTP-1D-IRS-1 complex formation and PTP-1D tyrosine phosphorylation and activation. Our findings show that the tyrosine phosphorylation of IRS-1 and PTP-1D represents a convergent intracellular signaling cascade stimulated by both growth factor (i.e. IGF I) and G- protein.coupled (i.e. AT1) receptors.

Original languageEnglish (US)
Pages (from-to)12373-12379
Number of pages7
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - May 9 1997


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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