PROTEASE ACTIVATED RECEPTOR 3

描述：凝血酶是一种多功能丝氨酸蛋白酶，产生于 血管损伤的部位。它在体外对血小板、白细胞、 内皮细胞和间充质细胞提示凝血酶可能不仅介导 止血和血栓形成，但也有炎症和增殖反应 对体内血管损伤的影响。该应用程序的总体目标是 了解凝血酶信号，从而提供预防策略 对血管损伤的不良反应，如形成血小板血栓 覆盖破裂的动脉粥样硬化斑块，通常是不稳定的原因 心绞痛和心肌梗塞。第一种凝血酶--par1基因的敲除 受体，由S课题组克隆和鉴定，提供 小鼠体内存在第二凝血酶受体的确凿证据 对于不同凝血酶受体的组织特异性作用。 考夫林博士最近克隆并鉴定了第二种凝血酶Par3 在人类骨髓和小鼠巨核细胞中表达的受体。 该提案试图定义Par3在体内的作用和信号转导 它所利用的机制。调查员试图回答以下问题 问：Par1和Par3在人类血小板和其他组织中起什么作用 细胞？Par3对Par1/-小鼠血小板中的凝血酶信号有影响吗？ 或者还有其他的凝血酶受体存在？是信号机制吗 Par3使用的信令与Par1使用的不同，信令是什么 从Par3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?