p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils.
Author
Summary, in English
Neutrophil apoptosis occurs both in the bloodstream and in the tissue and is considered essential for the resolution of an inflammatory process. Here, we show that p38–mitogen-activated protein kinase (MAPK) associates to caspase-8 and caspase-3 during neutrophil apoptosis and that p38-MAPK activity, previously shown to be a survival signal in these primary cells, correlates with the levels of caspase-8 and caspase-3 phosphorylation. In in vitro experiments, immunoprecipitated active p38-MAPK phosphorylated and inhibited the activity of the active p20 subunits of caspase-8 and caspase-3. Phosphopeptide mapping revealed that these phosphorylations occurred on serine-364 and serine-150, respectively. Introduction of mutated (S150A), but not wild-type, TAT-tagged caspase-3 into primary neutrophils made the Fas-induced apoptotic response insensitive to p38-MAPK inhibition. Consequently, p38-MAPK can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response. This research was originally published in
The Journal of Experimental Medicine.
The Journal of Experimental Medicine.
Department/s
Publishing year
2004
Language
English
Pages
449-458
Publication/Series
Journal of Experimental Medicine
Volume
199
Issue
4
Full text
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Document type
Journal article
Publisher
Rockefeller University Press
Topic
- Cancer and Oncology
- Medicinal Chemistry
Status
Published
Research group
- Molecular Pathology, Malmö
- Experimental Pathology, Malmö
ISBN/ISSN/Other
- ISSN: 1540-9538