The light chain of factor Va contains the activity of factor Va that accelerates protein C activation by thrombin.

Abstract

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 Va and VIIIa. 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 Va, a substrate for activated protein C, is also a thrombin cofactor in the activation of protein C (Salem, H.H., Broze, G.J., Miletich, J. P., and Majerus, P.W. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1584-1588). When factor Va is fractionated to its individual components, only the light chain (Mr 78,000) has thrombin cofactor activity. Although factor Va and thrombomodulin can both stimulate thrombin-catalyzed protein C activation, the physiological relationship between these two proteins remains to be determined.