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

Tang, Fengyuan; Gill, Jason; Ficht, Xenia Maria; Barthlott, Thomas; Cornils, Hauke; Schmitz-Rohmer, Debora; Hynx, Debby; Zhou, Dawang; Zhang, Lei; Xue, Gongda; Grzmil, Michal; Yang, Zhongzhou; Hergovich, Alexander; Hollaender, Georg A; Stein, Jens Volker; Hemmings, Brian A; Matthias, Patrick (2015). The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility. Science signaling, 8(397), ra100. American Association for the Advancement of Science 10.1126/scisignal.aab2425

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Ficht, Xenia Maria and Stein, Jens Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1937-9145

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

14 Mar 2016 15:13

Last Modified:

13 Dec 2017 15:40

Publisher DOI:

10.1126/scisignal.aab2425

PubMed ID:

26443704

URI:

https://boris.unibe.ch/id/eprint/77342

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