Cleavage of protein S by a platelet membrane protease.
Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with approximately 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.
D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010447:Peptide Hydrolases / Q000097:blood*; D011480:Protease Inhibitors / Q000494:pharmacology; D017293:Protein S
D006023:Glycoproteins; D011480:Protease Inhibitors; D017293:Protein S; D010447:Peptide Hydrolases