Glucose-stimulated protein synthesis in pancreatic β-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP-Met-tRNAi) and the dephosphorylation of eIF2α

Gomez, E. and Powell, M.L. and Greenman, I.C. and Herbert, Terence (2004) Glucose-stimulated protein synthesis in pancreatic β-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP-Met-tRNAi) and the dephosphorylation of eIF2α. Journal of Biological Chemistry, 279 (52). pp. 53937-53946. ISSN 0021-9258

Full content URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Documents
T Herbert Glucose-stimulated.pdf
[img]
[Download]
[img]
Preview
PDF
T Herbert Glucose-stimulated.pdf - Whole Document
Available under License Creative Commons Attribution-NonCommercial 4.0 International.

450kB
Item Type:Article
Item Status:Live Archive

Abstract

In pancreatic β-cells, glucose causes a rapid increase in the rate of protein synthesis. However, the mechanism by which this occurs is poorly understood. In this report, we demonstrate, in the pancreatic β-cell line MIN6, that glucose stimulates the recruitment of ribosomes onto the mRNA, indicative of an increase in the rate of the initiation step of protein synthesis. This increase in the rate of initiation is not mediated through an increase in the availability of the initiation complex eIF4F, because glucose is unable to stimulate eIF4F assembly or, in the absence of amino acids, modulate the phosphorylation status of 4E-BP1. Moreover, in MIN6 cells and isolated islets of Langerhans, rapamycin, an inhibitor of the mammalian target of rapamycin, only partially inhibited glucose-stimulated protein synthesis. However, we show that glucose stimulates the dephosphorylation of eIF2α in MIN6 cells and the assembly of the translational ternary complex, eIF2-GTP·Met-tRNAi, in both MIN6 cells and islets of Langerhans. The changes in the phosphorylation of eIF2α are not mediated by the PKR-like endoplasmic reticulum eIF2α kinase (PERK), because PERK is not phosphorylated at low glucose concentrations and overexpression of a dominant negative form of PERK has no significant effect on either glucose-stimulated protein synthesis or the phosphorylation of eIF2α. Taken together, these results indicate that glucose-stimulated protein synthesis in pancreatic β-cells is regulated by a mechanism largely independent of the activity of mammalian target of rapamycin, but which is likely to be dependent on the availability of the translational ternary complex, regulated by the phosphorylation status of eIF2α.

Additional Information:cited By 40
Keywords:Glucose-stimulated, eIF2-GTP-Met-tRNAi
Subjects:B Subjects allied to Medicine > B290 Pharmacology, Toxicology and Pharmacy not elsewhere classified
Divisions:College of Science > School of Pharmacy
ID Code:28233
Deposited On:01 Aug 2018 09:28

Repository Staff Only: item control page