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 beta-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 1 receptor beta-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.
Du
J
J
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Sperling
L S
LS
Marrero
M B
MB
Phillips
L
L
Delafontaine
P
P
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D000804:Angiotensin II; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D013917:Thrombin; D019204:GTP-Binding Proteins