Protein C

Literature References: Vitamin K-dependent plasma protein involved in the regulation of hemostasis. Two-chain, multi-domain glycoprotein, mol wt ~62,000. Circulates as a zymogen; activated by thrombin complexed with thrombomodulin, q.v. Activated protein C is a serine protease that controls coagulation by the selective inactivation of factors Va and VIIIa. This activity is potentiated by factor V and by Protein S, a vitamin K-dependent protein unrelated to the serine proteases. Identification of autoprothrombin II-A, an anticoagulant obtained from purified prothrombin complex: E. F. Mammen et al., Thromb. Diath. Haemorrh. 5, 218 (1960). Purification: W. H. Seegers et al., Thromb. Res. 1, 443 (1972). Characterization: J. Stenflo, J. Biol. Chem. 251, 355 (1976). Identity with autoprothrombin II-A: W. H. Seegers et al., Thromb. Res. 8, 543 (1976). Isoln from human plasma: W. Kisiel, J. Clin. Invest. 64, 761 (1979). Amino acid sequence of bovine protein C: P. Fernlund, J. Stenflo, J. Biol. Chem. 257, 12170, 12180 (1982). Review of role in hemostasis: L. H. Clouse, P. C. Comp, N. Engl. J. Med. 314, 1298-1304 (1986); C. T. Esmon, J. Biol. Chem. 264, 4743-4746 (1989); of preparative methods and mechanism of activation: C. T. Esmon et al., Methods Enzymol. 222, 359-385 (1993). Review of protein C system and role in thromboembolic disease: B. Dahlbäck, Thromb. Res. 77, 1-43 (1995).

Literature References: Prepn: S. C. B. Yan et al., Biotechnology 8, 655-661 (1990). Review of development and clinical potential: S. B. Yan, B. W. Grinnell, Perspect. Drug Discovery Des. 1, 503-520 (1993). Clinical trial in severe sepsis: G. R. Bernard et al., N. Engl. J. Med. 344, 699 (2001).