Tissue factor-dependent factor VIIa signaling

Tissue factor (TF) is known primary as a cofactor for factor VIIa-mediated triggering of blood coagulation, which proceeds in a cascade of extracellul ar reactions. Recent investigations have, however, revealed that intracellu lar activities can also be induced by the proteolytic activity of factor VI Ia bound to cell surface TF. Factor VIIa signal transduction has thus been reported to induce mobilization of intracellular Ca2+ stores and p44/p42 MA PK phosphorylation and to result in expression of specific genes, which pre sumably affects a number of cellular functions. The factor VIIa-induced sig nal transduction is independent of the presence of the TF cytoplasmic domai n and it is distinctly different from signaling involving presently known p rotease-activated receptors (PARs) including receptors for thrombin and fac tor Xa. This short review summarizes recent advances in our understanding o f TF-dependent factor VIIa signaling. (Trends Cardiovasc Med 2000;10:47-52) . (C) 2000, Elsevier Science Inc.