ALPHA-THROMBIN STIMULATES SIS-INDUCING FACTOR-A DNA-BINDING ACTIVITY IN RAT AORTIC SMOOTH-MUSCLE CELLS

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