血小板活化聚集是血栓形成的关键原因，而整合素αIIbβ3是血小板活化聚集的最终共同通路，因此成为抗血栓研究的重点。前期工作发现，β3胞浆段模拟肽myr-RGT可与Src的SH3结合，通过解离β3与Src的相互作用而阻断外向内信号转导。这形成了一种新的抗血栓策略，可在保留血小板初期止血功能的基础上抑制其促血栓形成的能力，其应用前景已引起学术界重视。有关myr-RGT调控血小板功能的分子机制仍有一些关键环节亟待阐述。本项目旨在对RGT肽的作用机理进行下列深入探讨：一、RGT肽发挥干扰Src-β3相互作用的功能是否为膜靶定依赖性；二、Src与RGT肽结合后其包括活性在内的重要性质是否会发生改变；三、Src能否直接磷酸化β3胞浆段的Y747、Y759。上述研究将有助于更深入了解整合素αIIbβ3信号转导的分子机制，及更完整评估基于 RGT肽作用的抗血栓策略并对其后续应用研究提供指向性的判断依据。

Platelet activation and aggregation play central roles in thrombosis and integrin αIIbβ3 has been the focus of the anti-thrombotic research since it serves as a common pathway for all agonists to stimulate platelet activation and aggregation. Previous work has established that the myr-RGT peptide mimicking the C-terminal sequencees of the β3 cytoplasmic tail dissociates Src from β3 through binding to the SH3 domain of Src and thereby blocks outside-in signaling.This has invoked a new anti-thrombotic strategy in which the thrombotic potential of platelets is inhibited with an unaffected function in primary hemostasis. This concept has recently attracted significant attention of the scientific community as a promising therapeutic strategy for thrombotic diseases. However, several key molecular mechanisms by which the myr-RGT peptide regulates the platelet function remain largely unclear. This proposed study is directed towards understanding, firstly, whether the effect of the RGT peptide on Src-β3 interaction is membrane anchorage-dependent, secondly, whether the RGT peptide binding to Src alters the important features of Src including the kinase activity, and finally, whether Src is able to directly phosphorylate the Y747 and Y759 of the β3 cytoplasmic domain. Pursuit of this study would be of help in elucidating the molecular mechanisms of the signal transduction through integrin αIIbβ3 and evaluating the RGT-based anti-thrombotic strategy to provide directive information for its further application.