αIIbβ3 "由外向内"信号传导在稳定的血小板栓子形成过程中起关键作用，FcγRIIa在此信号通路中起重要作用，但对两者间的关系及随后的信号转导仍不清楚。我们预实验发现两者空间上接近、功能上相关，前期研究中申请者发现Lyn磷酸化PECAM-1分子中的ITIM，故申请者推测αIIbβ3和FcγRIIa或交联、或直接相连或以纤维蛋白原结合后的信号转导相互作用，且与αIIbβ3胞内段相连的SFKs参与FcγRIIa分子中ITAM的磷酸化及下游信号转导。本课题拟采用免疫共沉淀、荧光共振能量转移技术和双分子荧光互补技术来观察静息状态和激活状态下αIIbβ3与FcγRIIa间的空间关系，并利用FcγRIIa转基因小鼠和Lyn基因敲除小鼠研究Src家族激酶（SFKs，特别是Lyn）在其中的作用，以揭示FcγRIIa介导的αIIbβ3 "由外向内"信号转导机制，为开发新的抗栓药物提供理论基础和新的靶点。

αIIbβ3 outside-in signaling is critical for supporting stable platelet-platelet interactions and thrombus formation. FcγRIIa plays a key role in this pathway. But their functional and physical relationship and the downstream signal are unclear. Our preliminary data implied that αIIbβ3 and FcγRIIa were proximal in the membrane and functional coupling. We have found that Lyn phosphorylates immunoreceptor tyrosine-based inhibiting motif (ITIM) in PECAM-1. We speculate that αIIbβ3 and FcγRIIa are cross-linked, or associated directly or act each other by fibrinogen binding. And Src family kinases (SFKs) associated with αIIbβ3 contribute to the immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation in FcγRIIa. We will use co-IP, FRET and BiFC to study the relationship between αIIbβ3 and FcγRIIa. Using FcγRIIa transgenic mice and Lyn deficient mice, we aslo study the SFKs(especially Lyn ) role in this pathway. The project will find out the mechanisms of αIIbβ3 outside-in signaling mediated by FcγRIIa.And this will promote the devolopment of a new class of novel anti-thrombus agents and lead to find the new drug target.