Angiotensin ii stimulates the tyrosine phosphorylation and activation of irs-i and ftp-id in rat aortic smooth muscle cells

Angiotensin II (Ang II) and the insulin like growth factor I (IGF I) mediate similar intracctlular signaling events through cell surface receptors with different structural and biochemical properties. For example, in rat aortic smooth muscle (RASM) cells, we find that IGF I induces the tyrosinc phosphorylation of the insulin receptor substrate 1 (IRS-1) (a src-homology 2 (SH₂) domain containing docking protein) and the soluble SH₂ binding tyrosine phosphatasc PTP-1D In addition, IGF I also stimulates a complex formation between IRS-1 and PTP-1D and the enzymatic activity of the tyrosine phosphatasc. The vasoactive octapeptidc Ang II, acting via its G-protein coupled ATi receptor, also elicits a similar early signaling event in RASM cells. We demonstrate that Ang II (10 'M) induces the tyrosine phosphorylation of IRS-1 (3-4 fold increase, l min) and PTP-1D (3-4t fold increase, 5 min), the complex formation of PTP-1D and IRS-1, and the tyrosine phosphatasc activity of FTP-ID (3-4 fold, 5 min). Furthermore, whan we clcctroporatc anu-IRS-1 antibodies into RASM cells, the Ang ll-induced activation of FTP-ID and its complex formation with IRS-1 arc blocked These findings suggest that IRS-1 and FTP-1D are closely involved in early intraceUular IGF I and Ang U signalling events, hi addition, these results may also represent an alternative signaling pathway mediated by seven transmcmbranc G-protcin linked receptors like the Ang II AT! receptor, leading to cell growth and proliferation.