α-Thrombin Stimulates sis -Inducing Factor-A DNA Binding Activity in Rat Aortic Smooth Muscle Cells

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Abstract
Exposure of rat aortic vascular smooth muscle cells to α-thrombin resulted in the appearance of sis -inducing factor-A (SIF-A)-like DNA binding activity. This response to α-thrombin was delayed (detectable at 1 hour) compared with the rapid activation (15 to 30 minutes) by platelet-derived growth factor and the cytokine interleukin-6. α-Thrombin-induced SIF-A was sensitive to treatment with the tyrosine kinase inhibitor genistein. The thrombin inhibitor hirudin prevented the α-thrombin-mediated SIF-A induction. Cycloheximide had no effect on the ability of α-thrombin to induce SIF-A, suggesting that induction does not require new protein synthesis. α-Thrombin-induced SIF-A could be resolved into two additional subcomplexes termed SIF-A F and SIF-A S . Antibodies against Stat3 reacted with α-thrombin-induced SIF-A F , suggesting that Stat3 or a related protein is present in this subcomplex. Induction of SIF-A DNA binding activity may contribute to α-thrombin-mediated cellular responses, including wound healing, cell proliferation, and inflammation in the vasculature.