Document Detail

p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65.
MedLine Citation:
PMID:  16818494     Owner:  NLM     Status:  MEDLINE    
The stress-activated c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein (MAP) kinase (p38) regulate apoptosis induced by several forms of cellular insults. Potential targets for these kinases include members of the Bcl-2 family proteins, which mediate apoptosis generated through the mitochondria-initiated, intrinsic cell death pathway. Indeed, the activities of several Bcl-2 family proteins, both pro- and anti-apoptotic, are controlled by JNK phosphorylation. For example, the pro-apoptotic activity of Bim(EL), a member of the Bcl-2 family, is stimulated by JNK phosphorylation at Ser-65. In contrast, there is no reported evidence that p38-induced apoptosis is due to direct phosphorylation of Bcl-2 family proteins. Here we report evidence that sodium arsenite-induced apoptosis in PC12 cells may be due to direct phosphorylation of Bim(EL) at Ser-65 by p38. This conclusion is supported by data showing that ectopic expression of a wild type, but not a non-phosphorylatable S65A mutant of Bim(EL), potentiates sodium arsenite-induced apoptosis and by experiments showing direct phosphorylation of Bim(EL) at Ser-65 by p38 in vitro. Furthermore, sodium arsenite induced Bim(EL) phosphorylation at Ser-65, which was blocked by p38 inhibition. This study provides the first example whereby p38 induces apoptosis by phosphorylating a member of the Bcl-2 family and illustrates that phosphorylation of Bim(EL) on Ser-65 may be a common regulatory point for cell death induced by both JNK and p38 pathways.
Beibei Cai; Sandra H Chang; Esther B E Becker; Azad Bonni; Zhengui Xia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-07-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-28     Completed Date:  2006-10-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25215-22     Citation Subset:  IM    
Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195-7234, USA.
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MeSH Terms
Apoptosis Regulatory Proteins / chemistry*,  metabolism
Arsenites / pharmacology
Cell Survival
Enzyme Inhibitors / pharmacology
Membrane Proteins / chemistry*,  metabolism
Oxidative Stress
PC12 Cells
Protein Structure, Tertiary
Proto-Oncogene Proteins / chemistry*,  metabolism
Serine / chemistry
Sodium Compounds / pharmacology
p38 Mitogen-Activated Protein Kinases / metabolism,  physiology*
Grant Support
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Arsenites; 0/Bcl-2-like protein 11; 0/Enzyme Inhibitors; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Sodium Compounds; 13768-07-5/sodium arsenite; 56-45-1/Serine; EC Mitogen-Activated Protein Kinases

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