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Metadata

Name
Hippo kinases Mst1 and Mst2 sense and amplify IL-2R?STAT5 signaling in Treg cells to establish stable regulatory activity
Repository
Gene Expression Omnibus
Identifier
geo.series:GSE120711
Description
Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Tregs can respond to low levels of IL-2, but the mechanisms by which STAT5 is activated during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2?STAT5 activity in Tregs. Tregs had high Mst1 and Mst2 (Mst1?Mst2) activity that was crucial to prevent tumor resistance and autoimmunity. Mechanistically, Mst1?Mst2 sensed IL-2 signals to promote the STAT5 activation necessary for Treg cell homeostasis and lineage stability, and maintain the highly suppressive phophorylated-STAT5+ Treg cell subpopulation. Unbiased quantitative proteomics revealed an association of Mst1 with the cytoskeletal DOCK8?LRCHs module that shaped activity Rho-family GTPase Rac activity, which in turn mediated STAT5 activation in Tregs. Collectively, IL-2?STAT5 signaling critically depends upon Mst1?Mst2 functions to maintain a stable Treg cell pool and immune tolerance.
We used microarrays to compare the global transcription profiles of WT and Mst1/Mst2-null Treg cell populations
Data or Study Types
Expression profiling by array
Source Organization
National Center for Biotechnology Information
Access Conditions
available
Year
2018
Access Hyperlink
http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE120711

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