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p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils.

Alvarado-Kristensson, Maria LU ; Melander, Fredrik LU ; Leandersson, Karin LU ; Rönnstrand, Lars LU ; Wernstedt, Christer and Andersson, Tommy LU (2004) In Journal of Experimental Medicine 199(4). p.449-458
Abstract
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... (More)
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

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
199
issue
4
pages
449 - 458
publisher
Rockefeller University Press
external identifiers
  • pmid:14970175
  • wos:000189185600002
  • scopus:1242276248
ISSN
1540-9538
DOI
10.1084/jem.20031771
language
English
LU publication?
yes
id
d931f910-5a80-4e29-90d6-2fe3a4be8ce6 (old id 120489)
alternative location
http://www.jem.org/cgi/content/abstract/199/4/449
date added to LUP
2007-07-24 10:25:31
date last changed
2017-09-24 04:19:15
@article{d931f910-5a80-4e29-90d6-2fe3a4be8ce6,
  abstract     = {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<br/><br>
The Journal of Experimental Medicine.},
  author       = {Alvarado-Kristensson, Maria and Melander, Fredrik and Leandersson, Karin and Rönnstrand, Lars and Wernstedt, Christer and Andersson, Tommy},
  issn         = {1540-9538},
  language     = {eng},
  number       = {4},
  pages        = {449--458},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils.},
  url          = {http://dx.doi.org/10.1084/jem.20031771},
  volume       = {199},
  year         = {2004},
}