In the present study, we demonstrate that, in pancreatic β-cells, eIF2α (eukaryotic initiation factor 2α) phosphorylation in response to a decrease in glucose concentration is primarily mediated by the activation of PERK [PKR (protein kinase RNA activated)-like endoplasmic reticulum kinase]. We provide evidence that this increase in PERK activity is evoked by a decrease in the energy status of the cell via a potentially novel mechanism that is independent of IRE1 (inositol requiring enzyme 1) activation and the accumulation of unfolded nascent proteins within the endoplasmic reticulum. The inhibition of eIF2α phosphorylation in glucose-deprived cells by the overexpression of dominant-negative PERK or an N-terminal truncation mutant of GADD34 (growth-arrest and DNA-damage-inducible protein 34) leads to a 53% increase in the rate of total protein synthesis. Polysome analysis revealed that this coincides with an increase in the amplitude but not the number of ribosomes per mRNA, indicating that eIF2α dephosphorylation mobilizes hitherto untranslated mRNAs on to polysomes. In summary, we show that PERK is activated at low glucose concentrations in response to a decrease in energy status and that this plays an important role in glucose-regulated protein synthesis in pancreatic β-cells.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
March 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 27 2008
A decrease in cellular energy status stimulates PERK-dependent eIF2α phosphorylation and regulates protein synthesis in pancreatic β-cells
Edith Gomez;
Edith Gomez
1
*Department of Cell Physiology and Pharmacology, Faculty of Medicine and Biological Sciences, The Henry Wellcome Building, University of Leicester, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Mike L. Powell;
Mike L. Powell
1
*Department of Cell Physiology and Pharmacology, Faculty of Medicine and Biological Sciences, The Henry Wellcome Building, University of Leicester, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Alan Bevington;
Alan Bevington
†Department of Infection, Immunity and Inflammation, Faculty of Medicine and Biological Sciences, The Henry Wellcome Building, University of Leicester, University Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Terence P. Herbert
Terence P. Herbert
2
*Department of Cell Physiology and Pharmacology, Faculty of Medicine and Biological Sciences, The Henry Wellcome Building, University of Leicester, University Road, Leicester LE1 9HN, U.K.
2To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
October 08 2007
Revision Received:
November 13 2007
Accepted:
December 03 2007
Accepted Manuscript online:
December 03 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 410 (3): 485–493.
Article history
Received:
October 08 2007
Revision Received:
November 13 2007
Accepted:
December 03 2007
Accepted Manuscript online:
December 03 2007
Citation
Edith Gomez, Mike L. Powell, Alan Bevington, Terence P. Herbert; A decrease in cellular energy status stimulates PERK-dependent eIF2α phosphorylation and regulates protein synthesis in pancreatic β-cells. Biochem J 15 March 2008; 410 (3): 485–493. doi: https://doi.org/10.1042/BJ20071367
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |