Tissue Factor–Factor VIIa Signaling

Abstract

How does tissue factor (TF), whose principle role is to support clotting factor VIIa (FVIIa) in triggering the coagulation cascade, affect various pathophysiological processes? One of the answers is that TF interaction with FVIIa not only initiates clotting but also induces cell signaling via activation of G-protein–coupled protease activated receptors (PARs). Recent studies using various cell model systems and limited in vivo systems are beginning to define how TF–VIIa-induced signaling regulates cellular behavior. Signaling pathways initiated by both TF–VIIa protease activation of PARs and phosphorylation of the TF–cytoplasmic domain appear to regulate cellular functions. In the present article, we review the emerging data on the mechanism of TF-mediated cell signaling and how it regulates various cellular responses, with particular focus on TF–VIIa protease-dependent signaling. Recent studies show that tissue factor–factor VIIa, whose primary function is to initiate the clotting cascade, transduces cell signaling in various cell types. This brief review summarizes recent literature on potential mechanisms by which tissue factor–factor VIIa activates cell signaling, and how tissue factor–factor VIIa-induced cell signaling may affect various pathophysiological processes.