IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v385y1997i6614d10.1038_385350a0.html
   My bibliography  Save this article

Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3

Author

Listed:
  • Hiroshi Nishina

    (University of Toronto)

  • Klaus D. Fischer

    (Mount Sinai Hospital
    University of Wuerzburg)

  • Laszlo Radvanyi

    (University of Toronto)

  • Arda Shahinian

    (University of Toronto)

  • Razqallah Hakem

    (University of Toronto)

  • Elizabeth A. Rubie

    (University of Toronto)

  • Alan Bernstein

    (Mount Sinai Hospital)

  • Tak W. Mak

    (University of Toronto)

  • James R. Woodgett

    (University of Toronto)

  • Josef M. Penninger

    (University of Toronto)

Abstract

Distinct and evolutionarily conserved signal transduction cascades mediate survival or death in response to developmental and environmental cues. The stress-activated protein kinases, or Jun N-terminal kinases (SAPKs/JNKs)1,2, are activated in response to a variety of cellular stresses such as changes in osmolarity and metabolism, DNA damage, heat shock, ischaemia, or inflammatory cytokines3–6. Sek1 (JNKK/MKK4) is a direct activator of SAPKs/JNKs in response to environmental stresses or mitogenic factors7–9. Here we investigate the role of Sek1 in development and apoptosis by deleting sek1 in embryonic stem (ES) cells by homologous recombination. We provide genetic evidence that different stresses utilize distinct signalling pathways for SAPK/ JNK activation, sek1−/− /rag2−/− chimaeric mice have normal numbers of mature T cells but fewer immature CD4+CD8+ thymocytes. The sek1 mutation did not affect the induction of apoptosis in response to environmental stresses in ES and T cells: instead, sek1 protected thymocytes from CD95 (Fas)- and CD3-mediated apoptosis. These data indicate that SEK1 mediates survival signals in T-cell development.

Suggested Citation

  • Hiroshi Nishina & Klaus D. Fischer & Laszlo Radvanyi & Arda Shahinian & Razqallah Hakem & Elizabeth A. Rubie & Alan Bernstein & Tak W. Mak & James R. Woodgett & Josef M. Penninger, 1997. "Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3," Nature, Nature, vol. 385(6614), pages 350-353, January.
    • Handle: RePEc:nat:nature:v:385:y:1997:i:6614:d:10.1038_385350a0
    DOI: 10.1038/385350a0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/385350a0
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/385350a0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:385:y:1997:i:6614:d:10.1038_385350a0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.