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 binding activity. This response to alpha-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. alpha-Thrombin-induced SIF-A was sensitive to treatment with the tyrosine kinase 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 induction does not require new protein synthesis. alpha-Thrombin-induced SIF-A could be resolved into two additional subcomplexes termed SIF-A, and SIF-As. Antibodies against Stat3 reacted with alpha-thrombin-induced SIF-Af, suggesting that Stat3 or a related protein is present in this subcomplex. Induction of SIF-A DNA binding activity may contribute to alpha-thrombin-mediated cellular responses, including wound healing, cell proliferation, and inflammation in the vasculature.
Bhat
G J
GJ
Weis Center for Research, Geisinger Clinic, Danville, Pa 17822, USA.
Abraham
S T
ST
Singer
H A
HA
Baker
K M
KM
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D050796:STAT3 Transcription Factor; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015534:Trans-Activators / Q000032:analysis
D004268:DNA-Binding Proteins; D006629:Hirudins; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D013917:Thrombin