The light chain of factor V(a) contains the activity of factor V(a) that accelerates protein C activation by thrombin

Protein C, a vitamin K-dependent protein, circulates in plasma as an inactive precursor. Once activated, it possesses potent anticoagulant activity through the inactivation of factors V(a) and VIII(a). Thrombin, the only known physiologic activator of this protein, is catalytically inefficient. Thrombomodulin, a protein purified from rabbit lungs, has been reported to enhance protein C activation by thrombin. We have previously demonstrated that factor V(a), a substrate for activated protein C, is also a thrombin cofactor in the activation of protein C. When factor V(a) is fractionated to its individual components, only the light chain (M(r) 78,000) has thrombin cofactor activity. Although factor V(a) and thrombomodulin can both stimulate thrombin-catalyzed protein C activation, the physiological relationship between these two proteins remains to be determined.