Eukaryotic initiation factor eIF2B and eukaryotic elongation factor eEF2 each mediate regulatory steps important for the overall regulation of mRNA translation in mammalian cells and are activated by insulin. Here, we demonstrate that their activation by insulin requires the presence, in the medium in which the cells are maintained, of both amino acids and glucose: insulin only induced activation of eIF2B and the dephosphorylation of eEF2 when cells were exposed to both types of nutrient. Other translational regulators, e.g. the 70 kDa ribosomal protein S6 kinase (p70 S6 kinase) and the eIF4E binding protein 1, 4E-BP1, are also regulated by insulin but their control does not require glucose, only amino acids. The effects of nutrients on the activation of eIF2B do not reflect changes in the phosphorylation of eIF2 (and, by inference, operation of a kinase analogous to yeast Gcn2p), or a requirement for nutrients for inactivation of glycogen synthase kinase-3 or dephosphorylation of eIF2B. Nutrients did not affect the ability of insulin to activate protein kinase B. These data show that activation by insulin of p70 S6 kinase, which modulates the translation of specific mRNAs, depends on the availability of amino acids whereas regulation of factors involved in overall activation of translation (eIF2B, eEF2) requires both amino acids and glucose. These results add substantially to the emerging evidence that nutrients themselves modulate functions of mammalian cells and indicate that (i) nutrients modulate the activation of eIF2B and eEF2 through as-yet unidentified mechanisms and (ii) regulation of p70 S6 kinase and 4E-BP1 by insulin requires other inputs in addition to protein kinase B.
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December 1999
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Research Article|
November 24 1999
Nutrients differentially regulate multiple translation factors and their control by insulin
Linda E. CAMPBELL;
Linda E. CAMPBELL
1
1Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
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Xuemin WANG;
Xuemin WANG
1
1Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
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Christopher G. PROUD
Christopher G. PROUD
2
1Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
2To whom correspondence should be addressed (e-mail c.g.proud@dundee.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 06 1999
Revision Received:
August 17 1999
Accepted:
September 09 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (2): 433–441.
Article history
Received:
April 06 1999
Revision Received:
August 17 1999
Accepted:
September 09 1999
Citation
Linda E. CAMPBELL, Xuemin WANG, Christopher G. PROUD; Nutrients differentially regulate multiple translation factors and their control by insulin. Biochem J 1 December 1999; 344 (2): 433–441. doi: https://doi.org/10.1042/bj3440433
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