血小板活化导致的血栓是各类血管性疾病的共性终末事件，是心肌梗塞、脑梗塞等致死致残性重大疾病的直接原因。血小板颗粒分泌是调控血栓的关键细胞事件。综合Msn激酶家族成员MINK1是血小板致密颗粒分泌的关键调控分子的发现与进一步的预实验基础上，本项目提出假设，Msn家族激酶受到STRIPAK复合物中的磷酸酶PP2A调控，继而通过MAPK和PI3K-Akt通路联系SNARE家族靶向致密颗粒分泌，调控血栓。我们拟通过已经构建完成的多个基因敲除小鼠和分子生物学研究手段，明晰血小板致密颗粒分泌的信号网络，为心脑血管性疾病的发生发展提供新的分子标志及干预靶点。

A common end event of nearly all vascualr diseases is the formation of platelet thrombus, which is directly responsible for mortality and morbidity associated with major cardio-cerebrovascular diseases such as myocardial infarction and cerebral infarction. Secretion of platelet granules constitutes a vital step in regulating thrombus and vascular homeostasis. We have previously identified an important regulator of platelet dense granule secretion, namely MINK1, a member of Msn kinase family. Based on this finding and further experiments, we hypothesize that Msn kinase family may constitutes the central core of platelet dense granule secretion network. Activities of Msn kinases are regulated by phosphatase PP2A, which is co-localized with Msn kinases in STRIPAK kinase-phosphatase complex, and further targeting to SNARE protein family-mediated dense granule secretion through MAPK and PI3K-Akt pathways. This hypothesis will be tested both in vitro and in vivo, using multiple newly constructed knock-out mice models. This study will delineate the signal network regulating platelet dense granule secretion, and provide novel molecular markers and intervention targets for cardio-cerebrovascular diseases.