Publication Date:
1999-11-13
Description:
A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor-dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated apoptosis in neurons. Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element-binding protein) at serine 133. Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonni, A -- Brunet, A -- West, A E -- Datta, S R -- Takasu, M A -- Greenberg, M E -- NIHP30-HD18655/HD/NICHD NIH HHS/ -- P01 HD 24926/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 12;286(5443):1358-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10558990" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Brain-Derived Neurotrophic Factor/pharmacology
;
Carrier Proteins/genetics/metabolism
;
*Cell Survival
;
Cells, Cultured
;
Cerebellum/cytology
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Flavonoids/pharmacology
;
Insulin-Like Growth Factor I/pharmacology
;
MAP Kinase Kinase 1
;
*MAP Kinase Signaling System
;
Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism
;
Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
;
Mutation
;
Neurons/*cytology/metabolism
;
Phosphorylation
;
Phosphoserine/metabolism
;
*Protein-Serine-Threonine Kinases
;
Rats
;
Rats, Long-Evans
;
Recombinant Fusion Proteins/metabolism
;
Ribosomal Protein S6 Kinases/genetics/*metabolism
;
*Transcription, Genetic
;
Transfection
;
bcl-Associated Death Protein
;
ras Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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