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Molecular and Cellular Biology, March 2002, p. 1656-1663, Vol. 22, No. 6
0270-7306/02/$04.00+0 DOI: 10.1128/MCB.22.6.1656-1663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Phosphorylation of Eukaryotic Translation Initiation Factor 4E Is Critical for Growth
Pascal E. D. Lachance,1 Mathieu Miron,2 Brian Raught,2 Nahum Sonenberg,2 and Paul Lasko1*
Departments of Biology,1
Biochemistry, McGill University, Montréal, Québec, Canada H3A 1B12
Received 1 June 2001/
Returned for modification 10 July 2001/
Accepted 27 November 2001
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 eIF4ESer251Ala 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.
* Corresponding author. Mailing address: Department of Biology, McGill University, 1205 Ave. Docteur Penfield, Montréal, Québec, Canada H3A 1B1. Phone: (514) 398-6401. Fax: (514) 398-8051. E-mail: Paul_Lasko{at}maclan.mcgill.ca.
Molecular and Cellular Biology, March 2002, p. 1656-1663, Vol. 22, No. 6
0022-538X/02/$04.00+0 DOI: 10.1128/MCB.22.6.1656-1663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.