Mst kinase roles

Immunity https://doi.org/10.1016/j.immuni.2018.10.010 (2018)

Regulatory T cells (T_reg cells) require the cytokine IL-2 for their suppressive activity, yet T_reg cells are adapted to low concentrations of IL-2, which has prompted questions about how efficient use of IL-2 is achieved. In Immunity, Chi and colleagues show that T_reg cells utilize the Hippo signal-transduction pathway to amplify IL-2-mediated activation of the transcription factor STAT5. Kinase-inhibitor screens identify roles for the Hippo kinases Mst1 and Mst2 in T_reg cells. Mice with T_reg cell–specific loss of Mst1-Mst2 exhibit a scurfy-like autoimmune phenotype and die prematurely. Loss of Mst kinases impairs T_reg cell lineage stability and survival in response to IL-2. Mechanistically, Mst1 interacts with the actin cytoskeleton regulators DOCK8, LRCH and Rac1, which regulate T cell mobility. Consistent with that finding, Mst kinase–deficient T_reg cells display defective homing and positioning within lymphoid organs, in addition to defective activation of phosphorylated STAT5 that compromises their suppressor function.