G-protein and tyrosine kinase receptor cross-talk in rat aortic smooth muscle cells: Thrombin- and angiotensin II-induced tyrosine phosphorylation of insulin receptor substrate-1 and insulin-like growth factor 1 receptor

Insulin-like growth factor I is an autocrine/paracrine factor for vascular smooth muscle cells and is required for angiotensin II- and thrombin-induced mitogenesis. The insulin-like growth factor I-triggered signaling pathway involves autophosphorylation of the β-subunit of its tyrosine kinase receptor and phosphorylation of insulin receptor substrate-1, the latter providing binding sites for proteins with src homology-2 domains. In rat aortic smooth muscle cells we observed that both angiotensin II and thrombin induced rapid tyrosine phosphorylation of insulin receptor substrate-1. Our results also demonstrated that these mitogens rapidly stimulated phosphorylation of the insulin-like growth factor I receptor β-chain. These data demonstrate a novel interaction between the G-protein coupled angiotensin II and thrombin receptors and the tyrosine-kinase insulin-like growth factor I receptor.