PMID:19073936

Citation	Zhou, D, Medoff, BD, Chen, L, Li, L, Zhang, XF, Praskova, M, Liu, M, Landry, A, Blumberg, RS, Boussiotis, VA, Xavier, R and Avruch, J (2008) The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc. Natl. Acad. Sci. U.S.A. 105:20321-6
Abstract	The Mst1 and Mst2 protein kinases are the mammalian homologs of hippo, a major inhibitor of cell proliferation in Drosophila. Mst1 is most abundant in lymphoid tissues. Mice lacking Mst1 exhibit markedly reduced levels of the Mst1 regulatory protein Nore1B/RAPL in lymphoid cells, whereas Mst2 abundance is unaltered. Mst1-null mice exhibit normal T cell development but low numbers of mature naïve T cells with relatively normal numbers of effector/memory T cells. In vitro, the Mst1-deficient naïve T cells exhibit markedly greater proliferation in response to stimulation of the T cell receptor whereas the proliferative responses of the Mst1-null effector/memory T cell cohort is similar to wild type. Thus, elimination of Mst1 removes a barrier to the activation and proliferative response of naïve T cells. The levels of Mst1 and Nore1B/RAPL in wild-type effector/memory T cells are approximately 10% those seen in wild-type naïve T cells, which may contribute to the enhanced proliferative responses of the former. Freshly isolated Mst1-null T cells exhibit high rates of ongoing apoptosis, a likely basis for their low numbers in vivo; they also exhibit defective clustering of LFA-1, as previously observed for Nore1B/RAPL-deficient T cells. Among known Mst1 substrates, only the phosphorylation of the cell cycle inhibitory proteins MOBKL1A/B is lost entirely in TCR-stimulated, Mst1-deficient T cells. Mst1/2-catalyzed MOBKL1A/B phosphorylation slows proliferation and is therefore a likely contributor to the anti-proliferative action of Mst1 in naïve T cells. The Nore1B/RAPL-Mst1 complex is a negative regulator of naïve T cell proliferation.
Links	PubMed PMC2600581 Online version:10.1073/pnas.0810773105
Keywords	Adaptor Proteins, Signal Transducing/physiology; Animals; Cell Proliferation; Lymphocyte Activation; Mice; Phosphorylation; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/physiology; Receptors, Antigen, T-Cell/physiology; T-Lymphocytes/cytology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:STK4		GO:1904237: positive regulation of substrate-dependent cell migration, cell attachment to substrate	ECO:0000315:		P		Figure 4	complete CACAO 11065

References

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