Differential involvement of p38 mitogen-activated protein kinase kinases MKK3 and MKK6 in T-cell apoptosis
The p38 mitogen‐activated protein kinase (p38MAPK) is activated in response to various stimuli, including cellular stress, inflammatory cytokines and cell surface receptors. The activation of p38MAPK is predominantly mediated by the two upstream MAPK kinases MKK3 and MKK6. To study the role of the p...
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Published in | EMBO reports Vol. 3; no. 8; pp. 785 - 791 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.08.2002
Oxford University Press |
Subjects | |
Online Access | Get full text |
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Summary: | The p38 mitogen‐activated protein kinase (p38MAPK) is activated in response to various stimuli, including cellular stress, inflammatory cytokines and cell surface receptors. The activation of p38MAPK is predominantly mediated by the two upstream MAPK kinases MKK3 and MKK6. To study the role of the p38MAPK pathway in vivo, we generated Mkk6−/− mice. We examined whether T‐cell apoptosis is affected in these mice and in our previously reported Mkk3−/− mice. Strikingly, in vivo deletion of double positive thymocytes in Mkk6−/− mice was impaired, whereas Mkk3−/− mice showed no apparent abnormality. Conversely, CD4+T cells from Mkk3−/− but not from Mkk6−/− mice were resistant to activation‐induced cell death and cytokine‐withdrawal‐induced apoptosis. In peripheral CD4+T cells, MKK3 is induced upon stimulation, whereas MKK6 is downregulated. These results suggest a novel mechanism regulating T‐cell apoptosis differentially through the p38MAPK pathway by MKK3 and MKK6. |
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Bibliography: | ark:/67375/WNG-6TSVDZNG-2 ArticleID:EMBR105 istex:8B1AF7C83F7C8C5F58542C8D6CD80240034015AD ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY 10591, USA Present address: Department of Microbiology and Immunology, Shinshu University, School of Medicine, Matsumoto 390-8621, Japan Present address: INSERM, Unité de recherché U536, Institut du Fer à Moulin, Paris 75005, France Present address: Department of Immunology, University of Washington, Seattle, WA 98195, USA Corresponding author. Tel: +1 203 737 2216; Fax: +1 203 737 2958; E-mail: richard.flavell@yale.edu |
ISSN: | 1469-221X 1469-3178 |
DOI: | 10.1093/embo-reports/kvf153 |