Article
- The EMBO Journal (2006) 25, 1659 - 1668
- doi:10.1038/sj.emboj.7601047
Published online: 16 March 2006
Subject Categories:
mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin
Thurl E Harris1, An Chi2, Jeffrey Shabanowitz2, Donald F Hunt2, Robert E Rhoads3 and John C Lawrence Jr1
- Department of Pharmacology, University of Virginia, Charlottesville, VA, USA
- Department of Chemistry, University of Virginia, Charlottesville, VA, USA
- Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
Correspondence to:
John C Lawrence Jr, Department of Pharmacology, University of Virginia Health System, PO Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735, USA. Tel.: +1 434 924 1584; Fax: +1 434 982 3575; E-mail: jcl3p@virginia.edu
Received 19 January 2006; Accepted 22 February 2006
Abstract
Insulin stimulates protein synthesis by increasing translation initiation. This response is mediated by mTOR and is believed to result from 4EBP1 phosphorylation, which allows eIF4E to bind eIF4G. Here, we present evidence that mTOR interacts directly with eIF3 and that mTOR controls the association of eIF3 and eIF4G. Activating mTOR signaling with insulin increased by as much as five-fold the amount of eIF4G bound to eIF3. This novel effect was blocked by rapamycin and other inhibitors of mTOR, and it required neither eIF4E binding to eIF4G nor eIF3 binding to the 40S ribosomal subunit. The increase in eIF4G associated with eIF3 occurred rapidly and at physiological concentrations of insulin. Moreover, the magnitude of the response was similar to the increase in eIF4E binding to eIF4G produced by insulin. Thus, increasing eIF4G association with eIF3 represents a potentially important mechanism by which insulin, as well as amino acids and growth factors that activate mTOR, stimulate translation.
Keywords:
- eIF4E,
- 4EBP1,
- eIF4B,
- mRNA translation initiation,
- rapamycin
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