THE FUNCTIONS OF PROTEIN C

活化蛋白C是一种有效的抗凝剂， 纤维蛋白溶解 当凝血酶结合时，蛋白C的活化迅速发生 一种特异性内皮细胞表面受体血栓调节蛋白 血栓调节蛋白加速凝血酶催化的蛋白C活化， Ca++依赖性反应。 Ca ~（++）在蛋白C激活中的作用 将用蛋白C和蛋白C进行动力学分析， 作为底物的Gla结构域已被除去。 初步数据 表明蛋白C上存在高亲和力的Ca++结合位点 与Gla依赖性Ca++结合位点不同。 本网站将 通过平衡透析和固有荧光变化研究。 血栓调节蛋白通常是一种膜蛋白。 凝血酶催化蛋白 C激活通过血栓调节蛋白重建成 膜。 血栓调节蛋白重建成 膜将被确定，并研究脂质的特异性。 将重新评价复溶系统的动力学，以确定 脂质增强的性质。 血栓调节蛋白浓度 内皮细胞表面是未知的。 的单克隆抗体 将产生血栓调节蛋白，并用于确定 血栓调节蛋白分子/内皮细胞。 从动力学研究来看， 可以确定内皮细胞是否提供独特的特性 合成系统无法复制的。 人血栓调节蛋白将 如先前对兔所做的那样进行分离和表征 血栓调节蛋白 人蛋白C、人血栓调节蛋白的动力学研究 和人内皮细胞。 活化蛋白C 介导的抗凝活性没有完全表征。 虽然 活化蛋白C抑制因子Va，失活速率太慢 来解释抗凝作用。 蛋白S刺激因子Va 失活，但体外刺激的程度并不能解释 等离子体刺激。 低水平活化蛋白C的影响 对血浆中凝血酶原和因子V激活的时间过程的影响 并在纯化系统中进行监测，以确定蛋白C是否单独 或蛋白S影响凝血酶原激活发生前的延迟 或者它是否影响凝血酶原的速率和/或程度 消费 血小板支持活化蛋白C的能力 还将研究抗凝血活性。

Activated protein C is a potent anticoagulant which also stimulates fibrinolysis. Activation of protein C occurs rapidly when thrombin binds to a specific endothelial cell surface receptor, thrombomodulin. Thrombomodulin accelerates thrombin catalyzed protein C activation in a Ca++ dependent reaction. The role of Ca++ in the activation of protein C will be analyzed kinetically with both protein C and protein C from which the Gla domain has been removed as the substrate. Preliminary data suggests the presence of a high affinity Ca++ binding site on protein C distinct from the Gla dependent Ca++ binding sites. This site will be studied by equilibrium dialysis and by intrinsic fluorescence changes. Thrombomodulin is normally a membrane protein. Thrombin catalyzed protein C activation is accelerated by reconstitution of thrombomodulin into membranes. The conditions for reconstitution of thrombomodulin into membranes will be determined and the specificity of the lipids studied. The kinetics of the reconstituted system will be re-evaluated to determine the nature of the lipid enhancement. The thrombomodulin concentration on the endothelial cell surface is not known. A monoclonal antibody to thrombomodulin will be produced and used to determine the number of thrombomodulin molecules/endothelial cell. From kinetic studies it will be possible to determine if the endothelial cell provides unique properties which cannot be duplicated by synthetic systems. Human thrombomodulin will be isolated and characterized as done previously for rabbit thrombomodulin. Kinetic studies on human protein C, human thrombomodulin and human endothelial cells will be performed. Activated protein C mediated anticoagulant activity is not completely characterized. Although activated protein C inhibits factor Va the rate of inactivation is too slow to account for the anticoagulant effect. Protein S stimulates factor Va inactivation, but the extent of stimulation in vitro does not account for the plasma stimulation. The influence of low levels of activated protein C on the time course of both prothrombin and factor V activation in plasma and in purified systems will be monitored to determine if protein C alone or with protein S influences the lag before prothrombin activation occurs or whether it influences the rate and/or extent of prothrombin consumption. The ability of platelets to support activated protein C anticoagulant activity will also be investigated.