Rsk1 mediates a MEK-MAP kinase cell survival signal

226Citations
Citations of this article
53Readers
Mendeley users who have this article in their library.

Abstract

Background: Growth factors activate an array of cell survival signaling pathways. Mitogen-activated protein (MAP) kinases transduce signals emanating from their upstream activators MAP kinase kinases (MEKs). The MEK-MAP kinase signaling cassette is a key regulatory pathway promoting cell survival. The downstream effectors of the mammalian MEK-MAP kinase cell survival signal have not been previously described. Results: We identify here a pro-survival role for the serine/threonine kinase Rsk1, a downstream target of the MEK-MAP kinase signaling pathway. In cells that are dependent on interleukin-3 (IL-3) for survival, pharmacological inhibition of MEKs antagonized the IL-3 survival signal. In the absence of IL-3, a kinase-dead Rsk1 mutant eliminated the survival effect afforded by activated MEK. Conversely, a novel constitutively active Rsk1 allele restored the MEK-MAP kinase survival signal. Experiments in vitro and in vivo demonstrated that Rsk1 directly phosphorylated the pro-apoptotic protein Bad at the serine residues that, when phosphorylated, abrogate Bad's pro-apoptotic function. Constitutively active Rsk1 caused constitutive Bad phosphorylation and protection from Bad-modulated cell death. Kinase-inactive Rsk1 mutants antagonize Bad phosphorylation. Bad mutations that prevented phosphorylation by Rsk1 also inhibited Rsk1-mediated cell survival. Conclusions: These data support a model in which Rsk1 transduces the mammalian MEK-MAP kinase signal in part by phosphorylating Bad.

Cite

CITATION STYLE

APA

Shimamura, A., Ballif, B. A., Richards, S. A., & Blenis, J. (2000). Rsk1 mediates a MEK-MAP kinase cell survival signal. Current Biology, 10(3), 127–135. https://doi.org/10.1016/S0960-9822(00)00310-9

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free