PROTEASE ACTIVATED RECEPTOR 3

描述：凝血酶是一种多功能丝氨酸蛋白酶， 血管损伤部位。 它在体外对血小板，白细胞， 内皮细胞和间充质细胞表明凝血酶不仅可以介导 止血和血栓形成，而且还有炎症和增殖反应 对体内血管的损伤。 应用程序的总体目标是 了解凝血酶信号传导，从而提供预防 对血管损伤的不良反应，如血小板血栓的形成， 覆盖破裂的动脉粥样硬化斑块， 心绞痛和心肌梗塞。 敲除第一个凝血酶par 1 研究者小组克隆并鉴定了受体， 小鼠存在第二凝血酶受体的明确证据 血小板和不同凝血酶受体的组织特异性作用。 博士Coughlin最近克隆并鉴定了第二种凝血酶PAR 3， 在人骨髓和小鼠巨核细胞中表达的受体。 该提案试图定义par 3在体内的作用和信号传导。 它所使用的机制。 调查员试图回答以下问题 问题：par 1和par 3在人类血小板和其他细胞中的作用是什么？ 细胞？ par 3是否解释了par 1-/-小鼠血小板中的凝血酶信号传导 还是还有其他凝血酶受体存在 是信号机制 由par 3使用，不同于由par 1使用的那些，以及什么是信令 从par 3激活到血小板分泌和聚集的途径？

DESCRIPTION: Thrombin is a multifunctional serine protease generated at sites of vascular injury. Its in vitro actions on platelets, leukocytes, endothelial and mesenchymal cells suggest that thrombin may mediate not only hemostasis and thrombosis but also inflammatory and proliferative responses to vascular damage in vivo. The overall goal of the application is to understand thrombin signaling, thereby providing strategies to prevent unwanted responses to vascular injury such as formation of platelet thrombi overlying ruptured atherosclerotic plaques, the usual cause of unstable angina and myocardial infarction. Knockout of par1, the first thrombin receptor cloned and characterized by the investigator s group, provided definitive evidence for the existence of second thrombin receptor in mouse platelets and for tissue specific roles for distinct thrombin receptors. Dr. Coughlin recently cloned and characterized par3, a second thrombin receptor that is expressed in human bone marrow and mouse megakaryocytes. The proposal seeks to define the role of par3 in vivo and the signaling mechanisms that it utilizes. The investigator seeks to answer the following questions: What are the roles of par1 and par3 in human platelets and other cells? Does par3 account for thrombin signaling in par1 -/- mouse platelets or do still other thrombin receptors exist? Are the signaling mechanisms utilized by par3 distinct from those used by par1, and what is the signaling pathway from par3 activation to platelet secretion and aggregation?