title: Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells.
abstract: 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 course. 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.
authors.affiliation: Departments of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Ali
authors.forename: B
authors.initials: B
authors.lastname: Schieffer
authors.forename: P
authors.initials: P
authors.lastname: Delafontaine
authors.forename: K E
authors.initials: KE
authors.lastname: Bernstein
authors.forename: B N
authors.initials: BN
authors.lastname: Ling
authors.forename: M B
authors.initials: MB
authors.lastname: Marrero
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D018274:Electroporation; D004789:Enzyme Activation; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000906:Antibodies; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; D046911:Macromolecular Substances; D010750:Phosphoproteins; D000804:Angiotensin II; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat