Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1

Biochem J. 2001 Sep 1;358(Pt 2):497-503. doi: 10.1042/0264-6021:3580497.

Abstract

The eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP1) interacts directly with eIF4E and prevents it from forming initiation factor (eIF4F) complexes required for the initiation of cap-dependent mRNA translation. Insulin and other agents induce the phosphorylation of 4E-BP1 at multiple sites, resulting in its release from eIF4E, and this involves signalling through the mammalian target of rapamycin (mTOR). Here we show that D-glucose promotes the ability of insulin to bring about the phosphorylation of 4E-BP1 and the formation of eIF4F complexes. This appears to involve facilitation of the phosphorylation of at least three phosphorylation sites on 4E-BP1, i.e. Thr-36, Thr-45 and Thr-69. Non-metabolizable glucose analogues cannot substitute for D-glucose, but other hexoses can. This suggests that a product of hexose metabolism mediates the permissive effect of glucose. The effect of glucose was concentration-dependent within the range 1-5 mM. In contrast with the situation for 4E-BP1, glucose does not allow full activation of the 70 kDa ribosomal protein S6 kinase (p70 S6k; another target of mTOR signalling) or phosphorylation, in vivo, of its substrate, ribosomal protein S6. Taken together with earlier data showing that amino acids regulate 4E-BP1 and p70 S6k, the present findings show that 4E-BP1 in particular is regulated in response to the availability of both amino acids and sugars.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Carbohydrate Metabolism
  • Carrier Proteins / metabolism*
  • Cricetinae
  • Eukaryotic Initiation Factor-2 / metabolism
  • Glucose / pharmacology*
  • Hexoses / physiology
  • Insulin / pharmacology
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Biosynthesis
  • Protein Kinases / physiology
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases

Substances

  • Carrier Proteins
  • Eukaryotic Initiation Factor-2
  • Hexoses
  • Insulin
  • Phosphoproteins
  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Glucose