The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex
The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex
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DOI：
10.1073/pnas.93.19.10212
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发表时间：
1996-09-17
影响因子：
11.1
通讯作者：
Esmon, CT
中科院分区：
文献类型：
--
作者：
StearnsKurosawa, DJ;Kurosawa, S;Esmon, CT
内皮细胞表面的蛋白C活化对血液凝固的负调节至关重要。我们现在证明，阻断蛋白C与内皮细胞蛋白C受体（EPCR）结合的单克隆抗体可降低内皮细胞上凝血酶-血栓调节蛋白复合物对蛋白C的激活率，但不阻断蛋白C结合而与EPCR结合的抗体则无影响。阻断EPCR-蛋白C相互作用的动力学结果是活化的表观Km增加，而不改变凝血酶对血栓调节蛋白的亲和力。缺乏γ-羧基谷氨酸结构域的蛋白C衍生物的活化速率不被抗EPCR抗体改变，γ-羧基谷氨酸结构域是与EPCR结合所需的。这些数据表明，蛋白C激活复合物涉及蛋白C，凝血酶，血栓调节蛋白，和EPCR。这些观察开启了关于血管内皮上凝血反应的控制的新问题。
Protein C activation on the surface of the endothelium is critical to the negative regulation of blood coagulation. We now demonstrate that monoclonal antibodies that block protein C binding to the endothelial cell protein C receptor (EPCR) reduce protein C activation rates by the thrombin-thrombomodulin complex on endothelium, but that antibodies that bind to EPCR without blocking protein C binding have no effect. The kinetic result of blocking the EPCR-protein C interaction is an increased apparent K-m for the activation without altering the affinity of thrombin for thrombomodulin. Activation rates of the protein C derivative lacking the gamma-carboxyglutamic acid domain, which is required for binding to EPCR, are not altered by the anti-EPCR antibodies. These data indicate that the protein C activation complex involves protein C, thrombin, thrombomodulin, and EPCR. These observations open new questions about the control of coagulation reactions on vascular endothelium.