Mitchell C A, Salem H H
J Clin Invest. 1987 Feb;79(2):374-9. doi: 10.1172/JCI112822.
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.
蛋白S是丝氨酸蛋白酶活化蛋白C的一种维生素K依赖性糖蛋白辅因子。在本研究中，我们证明125I-蛋白S以时间和钙依赖性的饱和反应与未刺激的血小板结合。半数最大结合发生在蛋白S浓度为10 nM时，每个血小板约有1100个结合位点。蛋白S与血小板结合后，由局限于血小板膜的蛋白酶介导对该蛋白进行快速切割。膜蛋白酶依赖于Ca++，受高浓度二异丙基氟磷酸抑制，但对多种其他蛋白酶抑制剂具有抗性。功能研究表明，蛋白S的切割与辅因子抗凝活性的完全丧失有关。我们得出结论，蛋白S与血小板结合并被一种新型的Ca++依赖性膜蛋白酶灭活。这可能代表一种调节蛋白S活性的生理反应。
