Abstract
Activation of the blood coagulation system is initiated by the binding of factor VIIa to tissue factor, which is de-encrypted on the injured endothelial cells and many other extravascular cells. A most importantcoagulation protease, thrombin, is a multifunctional protein that has, besides its function in hemostasis and thrombosis, many cellular effects that link the coagulation system with the inflammatory response, such as wound healing, atherosclerosis, angiogenesis, tumor cell growth and metastasis. Recent studies elucidated the receptor proteins for thrombin-mediated cell activation. The receptor was named as protease-activated receptor-1 (PAR-1). The subsequent studies led to the identification of the other PARs : PAR-2, PAR-3 and PAR-4. PAR-1 is activated not only by thrombin butalso by factor Xa, the tissue factor-factor VIIa complex and activated protein C in concert with endothelial protein C receptor. PAR-2 is activated by factor Xa, the tissue factor-factor VIIa complex, or the tissue factor-factor VIIa-factor Xa com-plex. PAR-3 and PAR-4 can also be activated by thrombin. In the PAR activation by the factor VIIa-tissue factor complex, the intracellular domain of the tissue factor itself may play important roles in the expression of specific cellular response in several physiological processes and in the pathogenesis of several diseases.
