Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bonni, A; Brunet, A; West, AE; Datta, SR; Takasu, MA; Greenberg, ME

Published Date

  • November 1999

Published In

Volume / Issue

  • 286 / 5443

Start / End Page

  • 1358 - 1362

PubMed ID

  • 10558990

Pubmed Central ID

  • 10558990

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.286.5443.1358

Language

  • eng