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

Patel, J., Wang, X.M. and Proud, C.G. (2001) Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1. Biochemical Journal, 358 (3), 497-503.

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 1–5mM. In contrast with the situation for 4E-BP1, glucose does not allow full activation of the 70kDa 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.

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