Article
- The EMBO Journal (2006) 25, 2781 - 2791
- doi:10.1038/sj.emboj.7601166
Published online: 8 June 2006
Subject Categories:
The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity
David Shahbazian1, Philippe P Roux2, Virginie Mieulet3, Michael S Cohen4, Brian Raught5, Jack Taunton4, John WB Hershey6, John Blenis2, Mario Pende3 and Nahum Sonenberg1
- Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
- Department of Cell Biology, Harvard Medical School, Boston, MA, USA
- INSERM, Avenir, U584, Université Paris 5, Faculté de Médecine Necker-Enfants Malades, Paris, France
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA
- Ontario Cancer Institute and McLaughlin Centre for Molecular Medicine, MaRS Centre, Toronto, Ontario, Canada
- Department of Biological Chemistry, School of Medicine, University of California, Davis, CA, USA
Correspondence to:
Nahum Sonenberg, Department of Biochemistry, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Rm. 807, Montreal, Quebec, Canada H3G 1Y6. Tel.: +1 514 398 7274; Fax: +1 514 398 1287; E-mail: nahum.sonenberg@mcgill.ca
Received 12 September 2005; Accepted 4 May 2006
Abstract
The eukaryotic translation initiation factor 4B (eIF4B) plays a critical role in recruiting the 40S ribosomal subunit to the mRNA. In response to insulin, eIF4B is phosphorylated on Ser422 by S6K in a rapamycin-sensitive manner. Here we demonstrate that the p90 ribosomal protein S6 kinase (RSK) phosphorylates eIF4B on the same residue. The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics. The S6K and RSK proteins are members of the AGC protein kinase family, and require PDK1 phosphorylation for activation. Consistent with this requirement, phosphorylation of eIF4B Ser422 is abrogated in PDK1 null embryonic stem cells. Phosphorylation of eIF4B on Ser422 by RSK and S6K is physiologically significant, as it increases the interaction of eIF4B with the eukaryotic translation initiation factor 3.
Keywords:
- crosstalk,
- eIF4B,
- phosphorylation,
- signaling,
- translation
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
The RSK family of kinases: emerging roles in cellular signalling
Nature Reviews Molecular Cell Biology Review (01 Oct 2008)
Molecular mechanisms of mTOR-mediated translational control
Nature Reviews Molecular Cell Biology Review (01 May 2009)
RESEARCH
AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B
Oncogene Original Article
Regulation of elongation factor 2 kinase by p90 RSK1 and p70 S6 kinase
The EMBO Journal Article (15 Aug 2001)
Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
The EMBO Journal Article (21 Apr 2004)
