The MTOR/PI3K and MAPK Pathways Converge on EIF4B to Control Its Phosphorylation and Activity

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Jun 10

PMID 16763566

Citations 242

Authors

David Shahbazian

Philippe P Roux

Virginie Mieulet

Michael S Cohen

Brian Raught

Jack Taunton

John W B Hershey

John Blenis

Mario Pende

Nahum Sonenberg

Affiliations

Soon will be listed here.

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.

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