title: Phosphorylation of eukaryotic translation initiation factor 4E is critical for growth.
abstract: Eukaryotic translation initiation factor 4E (eIF4E) binds to the cap structure at the 5' end of mRNAs and is a critical target for the control of protein synthesis. eIF4E is phosphorylated in many systems in response to extracellular stimuli, but biochemical evidence to date has been equivocal as to the biological significance of this modification. Here we use a genetic approach to this problem. We show that, in Drosophila melanogaster, homozygous eIF4E mutants arrest growth during larval development. In Drosophila eIF4EI, Ser251 corresponds to Ser209 of mammalian eIF4E, which is phosphorylated in response to extracellular signals. We find that, in vivo, eIF4EI Ser251 mutants cannot incorporate labeled phosphate. Furthermore, transgenic Drosophila organisms expressing eIF4E(Ser251Ala) in an eIF4E mutant background have reduced viability. Escapers develop more slowly than control siblings and are smaller. These genetic data provide evidence that eIF4E phosphorylation is biologically significant and is essential for normal growth and development.
authors.affiliation: Department of Biology, McGill University, 1205 Ave. Docteur Penfield, Montréal, Québec, Canada H3A 1B1.
authors.forename: Pascal E D
authors.initials: PE
authors.lastname: Lachance
authors.forename: Mathieu
authors.initials: M
authors.lastname: Miron
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Paul
authors.initials: P
authors.lastname: Lasko
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D039561:Eukaryotic Initiation Factor-4E; D005123:Eye / Q000254:growth & development; D005124:Eye Abnormalities / Q000235:genetics; D005328:Fetal Viability / Q000235:genetics; D005804:Genes, Lethal; D006720:Homozygote; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D014921:Wings, Animal / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors