The protein C anticoagulant pathway

C T Esmon
1992 Arteriosclerosis and Thrombosis A Journal of Vascular Biology  
Although protein C was described as an anticoagulant in 1960 by Dr. Seegers and colleagues, 1 widespread appreciation of the complexity of its activation, function, and physiological roles did not begin to develop until Stenflo independently characterized protein C as a vitamin K-dependent zymogen 2 that could be converted to a serine protease capable of membrane binding (Esmon et al 3 ). The subsequent demonstrations by Kisiel et al 4 that activated protein C was an anticoagulant that
more » ... ulant that inactivated factor V and by Walker et al 5 that the enzyme showed a marked specificity for factor Va provided information on the mechanism of action and the specificity of the enzyme. These observations were quickly extended when Vehar and Davie 6 observed that factor VIII was a substrate for activated protein C and that factor VEHa was the preferred substrate. Although the broad functions of the system were now clearly established, physiological activators were yet to be described, and the role of this system in the pathogenesis of thrombotic disease and in normal control of hemostasis remained to be investigated.
doi:10.1161/01.atv.12.2.135 fatcat:hhpz23lsgrauvmg3zxc7jmxmmm