PMID- 11513750
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20211203
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 358
IP  - Pt 2
DP  - 2001 Sep 1
TI  - Glucose exerts a permissive effect on the regulation of the initiation factor 4E 
      binding protein 4E-BP1.
PG  - 497-503
AB  - 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.
FAU - Patel, J
AU  - Patel J
AD  - Division of Molecular Physiology, School of Life Sciences, MSI/WTB Complex, Dow 
      Street, University of Dundee, Dundee DD1 5EH, Scotland, UK.
FAU - Wang, X
AU  - Wang X
FAU - Proud, C G
AU  - Proud CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Carrier Proteins)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Hexoses)
RN  - 0 (Insulin)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Carbohydrate Metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cricetinae
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Glucose/*pharmacology
MH  - Hexoses/physiology
MH  - Insulin/pharmacology
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Protein Kinases/physiology
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC1222084
EDAT- 2001/08/22 10:00
MHDA- 2001/10/05 10:01
PMCR- 2002/03/01
CRDT- 2001/08/22 10:00
PHST- 2001/08/22 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/08/22 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - 10.1042/0264-6021:3580497 [doi]
PST - ppublish
SO  - Biochem J. 2001 Sep 1;358(Pt 2):497-503. doi: 10.1042/0264-6021:3580497.