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PMID: 9878069 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E.

The EMBO journal ·Vol. 18 ·No. 1 ·1999-01-04 ·Pages 270-9

Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N

Abstract

Human eukaryotic translation initiation factor 4E (eIF4E) binds to the mRNA cap structure and interacts with eIF4G, which serves as a scaffold protein for the assembly of eIF4E and eIF4A to form the eIF4F complex. eIF4E is an important modulator of cell growth and proliferation. It is the least abundant component of the translation initiation machinery and its activity is modulated by phosphorylation and interaction with eIF4E-binding proteins (4E-BPs). One strong candidate for the eIF4E kinase is the recently cloned MAPK-activated protein kinase, Mnk1, which phosphorylates eIF4E on its physiological site Ser209 in vitro. Here we report that Mnk1 is associated with the eIF4F complex via its interaction with the C-terminal region of eIF4G. Moreover, the phosphorylation of an eIF4E mutant lacking eIF4G-binding capability is severely impaired in cells. We propose a model whereby, in addition to its role in eIF4F assembly, eIF4G provides a docking site for Mnk1 to phosphorylate eIF4E. We also show that Mnk1 interacts with the C-terminal region of the translational inhibitor p97, an eIF4G-related protein that does not bind eIF4E, raising the possibility that p97 can block phosphorylation of eIF4E by sequestering Mnk1.

MeSH Terms
Animals Binding Sites Cell Line Eukaryotic Initiation Factor-4E Eukaryotic Initiation Factor-4G Humans In Vitro Techniques Intracellular Signaling Peptides and Proteins Mice Models, Biological Peptide Initiation Factors/genetics,metabolism Phosphorylation Point Mutation Protein Binding Protein Serine-Threonine Kinases/metabolism Transfection
Chemicals
Eukaryotic Initiation Factor-4E Eukaryotic Initiation Factor-4G Intracellular Signaling Peptides and Proteins Peptide Initiation Factors eukaryotic translational regulator p97 MKNK1 protein, human Mknk1 protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pyronnet S
Department of Biochemistry and McGill Cancer Cancer Center, McGill University, 3655 Drummond Street, Montréal, Québec, H3G 1Y6 Canada.
Imataka H
Gingras A C
Fukunaga R
Hunter T
Sonenberg N
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.1.270
Published
1999-01-04
Pages
270-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171121
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.1.270 PMC Full Text View journal details
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