uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils
Show others and affiliations
2004 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 199, no 4, 449-458 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2004. Vol. 199, no 4, 449-458 p.
Keyword [en]
Apoptosis, Caspases/antagonists & inhibitors/*blood, Cell Survival/physiology, Humans, Inflammation/blood, Mitogen-Activated Protein Kinases/*blood, Neutrophils/cytology/*enzymology, Phosphorylation, Research Support; Non-U.S. Gov't, Signal Transduction/physiology, p38 Mitogen-Activated Protein Kinases
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72995DOI: 10.1084/jem.20031771PubMedID: 14970175OAI: oai:DiVA.org:uu-72995DiVA: diva2:100906
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2013-10-29Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=14970175&dopt=Citation

Search in DiVA

By author/editor
Wernstedt, Christer
By organisation
Ludwig Institute for Cancer Research
In the same journal
Journal of Experimental Medicine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 237 hits
ReferencesLink to record
Permanent link

Direct link