The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity

David Shahbazian; Philippe P. Roux; Virginie Mieulet; Michael S. Cohen; Brian Raught; Jack Taunton; John W.B. Hershey; John Blenis; Mario Pende; Nahum Sonenberg

doi:10.1038/sj.emboj.7601166

The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity

David Shahbazian, Philippe P. Roux, Virginie Mieulet, Michael S. Cohen, Brian Raught, Jack Taunton, John W.B. Hershey, John Blenis, Mario Pende, Nahum Sonenberg

Research output: Contribution to journal › Article › peer-review

423 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2781-2791
Number of pages	11
Journal	EMBO Journal
Volume	25
Issue number	12
DOIs	https://doi.org/10.1038/sj.emboj.7601166
State	Published - Jun 21 2006
Externally published	Yes

Keywords

Crosstalk
Phosphorylation
Signaling
Translation
eIF4B

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.1038/sj.emboj.7601166

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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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AU - Shahbazian, David

AU - Roux, Philippe P.

AU - Mieulet, Virginie

AU - Cohen, Michael S.

AU - Raught, Brian

AU - Taunton, Jack

AU - Hershey, John W.B.

AU - Blenis, John

AU - Pende, Mario

AU - Sonenberg, Nahum

PY - 2006/6/21

Y1 - 2006/6/21

N2 - 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.

AB - 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.

KW - Crosstalk

KW - Phosphorylation

KW - Signaling

KW - Translation

KW - eIF4B

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The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity

Abstract

Keywords

ASJC Scopus subject areas

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