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p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis.

Grethe, Simone LU and Ares, Isabella LU (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:
author
organization
publishing date
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
2007-07-25 09:37:43
date last changed
2019-11-10 03:45:34
@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},
  keyword      = {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},
  volume       = {18},
  year         = {2006},
}