RAC1
细胞生物学
激酶
罗亚
胸腺细胞
生物
磷酸化
基因剔除小鼠
CD8型
分子生物学
信号转导
免疫系统
免疫学
生物化学
受体
作者
Fan Mou,Maria Praskova,Fan Xia,Denille Van Buren,Hanno Hock,Joseph Avruch,Dawang Zhou
摘要
The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells. Compared with wild-type mice, these double knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in the circulation and in secondary lymphoid organs (SLOs). CD4+CD8− and CD4−CD8+ single-positive (SP) thymocytes in DKO mice resemble mature T cells of wild-type mice but undergo excessive apoptosis, and their egress from the thymus is reduced by >90%. Even when placed directly in the circulation, DKO SP thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2 abolished sphingosine-1 phosphate– and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1 or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes.
科研通智能强力驱动
Strongly Powered by AbleSci AI