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.