p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis.
(2006) In Cellular Signalling 18(4). p.531-540- Abstract
- We recently reported that p38 MAPK regulates TNF-induced endothelial apoptosis via phosphorylation and downregulation of Bcl-xL. Here, we describe that such apoptosis includes p38 NIAPK-mediated, protein phosphatase 2A (PP2A)-dependent, downregulation of the MEK-ERK pathway. Inhibition of PP2A with fostriecin or calyculin A significantly increased MEK phosphorylation, as did exposure to the p38 MAPK inhibitor SB203580. Inhibition of MEK potentiated TNF-induced caspase-3 activity and cell death, and both those events were suppressed by treatment with fostriecin or calyculin A. Immunoprecipitation experiments revealed an association between p38 MAPK, PP2A and MEK, and the results of a phosphatase assay suggested that PP2A is a downstream... (More)
- We recently reported that p38 MAPK regulates TNF-induced endothelial apoptosis via phosphorylation and downregulation of Bcl-xL. Here, we describe that such apoptosis includes p38 NIAPK-mediated, protein phosphatase 2A (PP2A)-dependent, downregulation of the MEK-ERK pathway. Inhibition of PP2A with fostriecin or calyculin A significantly increased MEK phosphorylation, as did exposure to the p38 MAPK inhibitor SB203580. Inhibition of MEK potentiated TNF-induced caspase-3 activity and cell death, and both those events were suppressed by treatment with fostriecin or calyculin A. Immunoprecipitation experiments revealed an association between p38 MAPK, PP2A and MEK, and the results of a phosphatase assay suggested that PP2A is a downstream target of p38 MAPK. Importantly, phosphorylation of Bad at Ser-112 was found to be regulated by p38 MAPK and PP2A. In summary, the present findings indicate a novel p38 MAPK-mediated apoptosis pathway, involving activation of Bad via PP2A-dependent inhibition of the MEK-ERK pathway. (c) 2005 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/139822
- author
- Grethe, Simone LU and Ares, Isabella LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- p38 MAP kinase, bad, apoptosis, endothelial cells, tumor necrosis, PP2A, factor alpha (TNF)
- in
- Cellular Signalling
- volume
- 18
- issue
- 4
- pages
- 531 - 540
- publisher
- Elsevier
- external identifiers
-
- wos:000234549600014
- pmid:15972258
- scopus:29044443481
- ISSN
- 1873-3913
- DOI
- 10.1016/j.cellsig.2005.05.023
- language
- English
- LU publication?
- yes
- id
- 0e906cc3-c38b-4bf9-92d0-1b8bded34736 (old id 139822)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15972258&query_hl=153
- date added to LUP
- 2016-04-01 12:37:25
- date last changed
- 2022-02-19 01:00:09
@article{0e906cc3-c38b-4bf9-92d0-1b8bded34736,
abstract = {{We recently reported that p38 MAPK regulates TNF-induced endothelial apoptosis via phosphorylation and downregulation of Bcl-xL. Here, we describe that such apoptosis includes p38 NIAPK-mediated, protein phosphatase 2A (PP2A)-dependent, downregulation of the MEK-ERK pathway. Inhibition of PP2A with fostriecin or calyculin A significantly increased MEK phosphorylation, as did exposure to the p38 MAPK inhibitor SB203580. Inhibition of MEK potentiated TNF-induced caspase-3 activity and cell death, and both those events were suppressed by treatment with fostriecin or calyculin A. Immunoprecipitation experiments revealed an association between p38 MAPK, PP2A and MEK, and the results of a phosphatase assay suggested that PP2A is a downstream target of p38 MAPK. Importantly, phosphorylation of Bad at Ser-112 was found to be regulated by p38 MAPK and PP2A. In summary, the present findings indicate a novel p38 MAPK-mediated apoptosis pathway, involving activation of Bad via PP2A-dependent inhibition of the MEK-ERK pathway. (c) 2005 Elsevier Inc. All rights reserved.}},
author = {{Grethe, Simone and Ares, Isabella}},
issn = {{1873-3913}},
keywords = {{p38 MAP kinase; bad; apoptosis; endothelial cells; tumor necrosis; PP2A; factor alpha (TNF)}},
language = {{eng}},
number = {{4}},
pages = {{531--540}},
publisher = {{Elsevier}},
series = {{Cellular Signalling}},
title = {{p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis.}},
url = {{http://dx.doi.org/10.1016/j.cellsig.2005.05.023}},
doi = {{10.1016/j.cellsig.2005.05.023}},
volume = {{18}},
year = {{2006}},
}