Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms
1999; American Association for the Advancement of Science; Volume: 286; Issue: 5443 Linguagem: Inglês
10.1126/science.286.5443.1358
ISSN1095-9203
AutoresAzad Bonni, Anne Brunet, Anne E. West, Sandeep Robert Datta, Mari A. Takasu, Michael E. Greenberg,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoA 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.
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