ANGIOTENSIN-II STIMULATES TYROSINE PHOSPHORYLATION AND ACTIVATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND PROTEIN-TYROSINE-PHOSPHATASE-1D IN VASCULAR SMOOTH-MUSCLE CELLS

Angiotensin II (Ang II) and insulin-like growth factor I (IGF I) stimu late intracellular signaling events through binding to their respectiv e G-protein-coupled and growth factor receptors. In rat aortic vascula r 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-bindi ng tyrosine phosphatase 1D (PTP-1D). In addition, IGF I stimulated PTP -1D phosphatase activity. Ang II (10(-7) M) also increased the tyrosin e phosphorylation of IRS-1 (4-fold), PTP-1D (5-fold), and PTP-1D activ ity (3-4-fold), but with a more transient time course. Ang II also ind uced 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 an d activation. Our findings show that the tyrosine phosphorylation of I RS-1 and PTP-1D represents a convergent intracellular signaling cascad e stimulated by both growth factor (i.e. IGF I) and G protein-coupled (i.e. AT(1)) receptors.