胶原蛋白途径导致的血小板活化是血栓形成的主要环节，阐明血小板活化机制对防治心脑血管血栓性疾病至关重要。糖蛋白VI（Glycoprotein VI，GPVI）是血小板最主要的胶原蛋白受体。血浆蛋白 Growth arrest specific gene 6（Gas6）的受体包括Tyro3、Axl和Mer。目前，关于Gas6受体调控GPVI介导的血小板活化的具体作用存在争议，有研究认为三者的作用相同，但是另有研究报道Gas6受体的作用甚微。为判定Gas6受体在GPVI介导的血小板活化的作用及分子机制，最近，我们应用单一Gas6受体基因敲除小鼠模型，发现Tyro3和Axl在GPVI介导的血小板活化中的作用更重要。本项目旨在更深入研究Gas6受体调控糖蛋白VI介导血小板活化的信号与分子机制，将为阐明血小板活化和血栓形成机制提供新的认识和研究思路，并为开发以Gas6受体为靶向的抗血栓新药研发提供资料

Collagen pathway is critical for platelet activation leading to thrombosis. It is important to understand the mechanism of platelet activation for the prevention and treatment of cardiovascular and cerebrovascular thrombotic diseases. Glycoprotein VI (GPVI) is the main collagen receptor on platelets. Tyro3, Axl, and Mer, three receptor tyrosine kinases are the receptors for plasma protein growth arrest specific gene 6 (Gas6) on platelets. Although several studies have indicated that Gas6 receptors regulate GPVI-mediated platelet activation, the role of each receptor remains controversial. Using single Gas6 receptor knockout mouse model, we have recently found Tyro3 and Axl, but not Mer, play more important role in GPVI-mediated platelet activation, suggesting that they are not euqally important. In this proposal, we plan to further investigate the signaling and molecular mechanisms underlying Gas6 receptor regulation of glycoprotein VI-mediated platelet activation. The results to be achieved will provide new insight into the mechanisms for platelet activation and thrombosis, and will provide the foundamental knowledge for the development of new antithrombotic drugs tartgeting Gas6 receptors.