p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils.
(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
The Journal of Experimental Medicine. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/120489
- author
- Alvarado-Kristensson, Maria LU ; Melander, Fredrik LU ; Leandersson, Karin LU ; Rönnstrand, Lars LU ; Wernstedt, Christer and Andersson, Tommy LU
- organization
- publishing date
- 2004
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010), Experimental Pathology (013031100)
- 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
- 2016-04-01 15:38:43
- date last changed
- 2022-12-04 18:12:55
@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 = {{https://lup.lub.lu.se/search/files/4439661/623951.pdf}}, doi = {{10.1084/jem.20031771}}, volume = {{199}}, year = {{2004}}, }