Regulation of activated protein C by thrombin-modified protein S.
Protein S, a vitamin K-dependent plasma protein having Gla-residues, increases the rate of inactivation of Factor Va by activated protein C by enhancing the binding of activated protein C to phospholipid [Walker, J.F. (1981) J. Biol. Chem. 256, 11128-11131]. The present study aimed at elucidating the effect of thrombin-modified protein S on Factor Va inactivation by activated protein C. Nondigested protein S consisted 81% of intact form and 19% of modified form, and thrombin-digested protein S had 96% modified form. Protein S, both nondigested and digested, did not show any effects on the amidolytic activity of activated protein C towards synthetic peptide substrate. Nondigested protein S stimulated the Factor Va inactivation by activated protein C, whereas the digested protein appeared to suppress the inactivation. Protein-phospholipid binding experiments showed that although nondigested protein S enhanced the binding of activated protein C to phospholipid stoichiometrically, digested protein S appeared to not only suppress the complex formation, but also dissociate the complex. This evidence suggested that protein S modified by thrombin regulates the action of activated protein C towards Factor Va on phospholipid.
D004789:Enzyme Activation; D005165:Factor V / Q000378:metabolism; D015943:Factor Va; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D046911:Macromolecular Substances; D011486:Protein C; D017293:Protein S; D013917:Thrombin / Q000378:metabolism*
D006023:Glycoproteins; D008081:Liposomes; D046911:Macromolecular Substances; D011486:Protein C; D017293:Protein S; D015943:Factor Va; D005165:Factor V; D013917:Thrombin