PMID- 12194824
OWN - NLM
STAT- MEDLINE
DCOM- 20030311
LR  - 20220228
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 12
IP  - 16
DP  - 2002 Aug 20
TI  - Activation of AMP-activated protein kinase leads to the phosphorylation of 
      elongation factor 2 and an inhibition of protein synthesis.
PG  - 1419-23
AB  - Protein synthesis, in particular peptide-chain elongation, consumes cellular 
      energy. Anoxia activates AMP-activated protein kinase (AMPK, see ), resulting in 
      the inhibition of biosynthetic pathways to conserve ATP. In anoxic rat 
      hepatocytes or in hepatocytes treated with 5-aminoimidazole-4-carboxamide (AICA) 
      riboside, AMPK was activated and protein synthesis was inhibited. The inhibition 
      of protein synthesis could not be explained by changes in the phosphorylation 
      states of initiation factor 4E binding protein-1 (4E-BP1) or eukaryotic 
      initiation factor 2alpha (eIF2alpha). However, the phosphorylation state of 
      eukaryotic elongation factor 2 (eEF2) was increased in anoxic and AICA 
      riboside-treated hepatocytes and in AICA riboside-treated CHO-K1 cells, and eEF2 
      phosphorylation is known to inhibit its activity. Incubation of CHO-K1 cells with 
      increasing concentrations of 2-deoxyglucose suggested that the mammalian target 
      of the rapamycin (mTOR) signaling pathway did not play a major role in 
      controlling the level of eEF2 phosphorylation in response to mild ATP depletion. 
      In HEK293 cells, transfection of a dominant-negative AMPK construct abolished the 
      oligomycin-induced inhibition of protein synthesis and eEF2 phosphorylation. 
      Lastly, eEF2 kinase, the kinase that phosphorylates eEF2, was activated in anoxic 
      or AICA riboside-treated hepatocytes. Therefore, the activation of eEF2 kinase by 
      AMPK, resulting in the phosphorylation and inactivation of eEF2, provides a novel 
      mechanism for the inhibition of protein synthesis.
FAU - Horman, Sandrine
AU  - Horman S
AD  - Hormone and Metabolic Research Unit, Christian de Duve International Institute of 
      Cellular Pathology and Universite Catholique de Louvain, Avenue Hippocrate, 75, 
      B-1200, Brussels, Belgium.
FAU - Browne, Gareth
AU  - Browne G
FAU - Krause, Ulrike
AU  - Krause U
FAU - Patel, Jigna
AU  - Patel J
FAU - Vertommen, Didier
AU  - Vertommen D
FAU - Bertrand, Luc
AU  - Bertrand L
FAU - Lavoinne, Alain
AU  - Lavoinne A
FAU - Hue, Louis
AU  - Hue L
FAU - Proud, Christopher
AU  - Proud C
FAU - Rider, Mark
AU  - Rider M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Oligomycins)
RN  - 0 (Peptide Elongation Factor 2)
RN  - 0 (Ribonucleosides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 53IEF47846 (acadesine)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/metabolism
MH  - Animals
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Deoxyglucose/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/metabolism
MH  - Hepatocytes/cytology/physiology
MH  - Humans
MH  - Multienzyme Complexes/genetics/*metabolism
MH  - Oligomycins/metabolism
MH  - Oxygen/metabolism
MH  - *Peptide Chain Elongation, Translational
MH  - Peptide Elongation Factor 2/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Rats
MH  - Ribonucleosides/metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2002/08/27 10:00
MHDA- 2003/03/12 04:00
CRDT- 2002/08/27 10:00
PHST- 2002/08/27 10:00 [pubmed]
PHST- 2003/03/12 04:00 [medline]
PHST- 2002/08/27 10:00 [entrez]
AID - S0960-9822(02)01077-1 [pii]
AID - 10.1016/s0960-9822(02)01077-1 [doi]
PST - ppublish
SO  - Curr Biol. 2002 Aug 20;12(16):1419-23. doi: 10.1016/s0960-9822(02)01077-1.