THE PROTEIN-C ANTICOAGULANT PATHWAY
THE PROTEIN-C ANTICOAGULANT PATHWAY
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DOI：
10.1161/01.atv.12.2.135
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发表时间：
1992-02-01
期刊：
影响因子：
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通讯作者：
ESMON, CT
中科院分区：
文献类型：
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作者：
ESMON, CT
虽然蛋白C在1960年被Seegers博士及其同事描述为抗凝剂，1但直到Stenflo独立地将蛋白C表征为维生素K依赖性酶原2，其可以转化为能够膜结合的丝氨酸蛋白酶（Esmon等人3），才开始对其激活、功能和生理作用的复杂性有了广泛的认识。随后Kisiel等人4证明活化蛋白C是一种使因子V失活的抗凝剂，步行者等人5证明该酶对因子Va显示出显著的特异性，这提供了关于该酶的作用机制和特异性的信息。当Vehar和Davie6观察到因子VIII是活化蛋白C的底物并且因子VEHa是优选底物时，这些观察结果迅速扩展。虽然该系统的广泛功能现已明确，但生理激活剂尚未被描述，该系统在血栓性疾病发病机制和正常止血控制中的作用仍有待研究。
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 zymogen2 that could be converted to a serine protease capable of membrane binding (Esmon et al3). The subsequent demonstrations by Kisiel et al4 that activated protein C was an anticoagulant that inactivated factor V and by Walker et al5 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 Davie6 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.