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Sci Signal. 2015 Oct 6;8(397):ra100. doi: 10.1126/scisignal.aab2425.

The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility.

Author information

1
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Department of Biomedicine, University of Basel, 4058 Basel, Switzerland. patrick.matthias@fmi.ch fengyuan.tang@fmi.ch.
2
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
3
Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
4
Laboratory of Pediatric Immunology, Department of Biomedicine, University of Basel and Basel University Children's Hospital, 4058 Basel, Switzerland.
5
State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, 361006 Xiamen, China.
6
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
7
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 210061 Nanjing, China.
8
UCL Cancer Institute, WC1E 6BT London, UK.
9
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Faculty of Science, University of Basel, 4003 Basel, Switzerland. patrick.matthias@fmi.ch fengyuan.tang@fmi.ch.

Abstract

The serine and threonine kinase MST1 is the mammalian homolog of Hippo. MST1 is a critical mediator of the migration, adhesion, and survival of T cells; however, these functions of MST1 are independent of signaling by its typical effectors, the kinase LATS and the transcriptional coactivator YAP. The kinase NDR1, a member of the same family of kinases as LATS, functions as a tumor suppressor by preventing T cell lymphomagenesis, which suggests that it may play a role in T cell homeostasis. We generated and characterized mice with a T cell-specific double knockout of Ndr1 and Ndr2 (Ndr DKO). Compared with control mice, Ndr DKO mice exhibited a substantial reduction in the number of naïve T cells in their secondary lymphoid organs. Mature single-positive thymocytes accumulated in the thymus in Ndr DKO mice. We also found that NDRs acted downstream of MST1 to mediate the egress of mature thymocytes from the thymus, as well as the interstitial migration of naïve T cells within popliteal lymph nodes. Together, our findings indicate that the kinases NDR1 and NDR2 function as downstream effectors of MST1 to mediate thymocyte egress and T cell migration.

PMID:
26443704
DOI:
10.1126/scisignal.aab2425
[Indexed for MEDLINE]

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