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The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. | LitMetric

AI Article Synopsis

  • The Mst1 kinase plays a crucial role in regulating T cell functions such as adhesion, migration, proliferation, and apoptosis in mice.
  • Double knockout mice lacking both Mst1 and Mst2 have significantly fewer mature T cells in their circulation and lymphoid organs compared to normal mice, with increased apoptosis among T cells.
  • The absence of Mst1 and Mst2 disrupts key signaling pathways, preventing the migration of developing thymocytes to secondary lymphoid organs and impairing their overall response to migration cues.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328371PMC
http://dx.doi.org/10.1084/jem.20111692DOI Listing

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