PMID- 14684182
OWN - NLM
STAT- MEDLINE
DCOM- 20040210
LR  - 20220225
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 313
IP  - 2
DP  - 2004 Jan 9
TI  - mTOR integrates amino acid- and energy-sensing pathways.
PG  - 443-6
AB  - The AMP-activated protein kinase (AMPK) exists as a heterotrimetric complex 
      comprising a catalytic alpha subunit and non-catalytic beta and gamma subunits. 
      Under conditions of hypoxia, exercise, ischemia, heat shock, and low glucose, 
      AMPK is activated allosterically by rising cellular AMP and by phosphorylation of 
      the catalytic alpha subunit. The mammalian target of rapamycin (mTOR) controls 
      cellular functions in response to amino acids and growth factors. Recent reports 
      including our study have demonstrated the possible interplay between mTOR and 
      AMPK signaling pathways, supporting a model in which mitochondrial dysfunction 
      caused by the mitochondrial inhibitors or ATP depletion inhibits activation of 
      p70 S6 kinase alpha (p70alpha), a downstream effector of mTOR, by activating 
      AMPK. Leucine may stimulate p70alpha phosphorylation via mTOR pathway, in part, 
      by serving both as a mitochondrial fuel through oxidative carboxylation and an 
      allosteric activation of glutamate dehydrogenase. This hypothesis may support an 
      idea in which leucine modulates mTOR function, in part by regulating 
      mitochondrial function and AMPK. Further understanding of the role of mTOR in 
      coordinating amino acid- and energy-sensing pathways would provide new insights 
      into relationship between nutrients and cellular functions.
FAU - Tokunaga, Chiharu
AU  - Tokunaga C
AD  - Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
FAU - Yoshino, Ken-ichi
AU  - Yoshino K
FAU - Yonezawa, Kazuyoshi
AU  - Yonezawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Amino Acids)
RN  - 0 (Multienzyme Complexes)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
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  - GMW67QNF9C (Leucine)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Amino Acids/*metabolism
MH  - Animals
MH  - Energy Metabolism/*physiology
MH  - Glucose/metabolism
MH  - Humans
MH  - Leucine/metabolism
MH  - Mitochondria/metabolism
MH  - Multienzyme Complexes/chemistry/metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/chemistry/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
RF  - 20
EDAT- 2003/12/20 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/12/20 05:00
PHST- 2003/12/20 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/12/20 05:00 [entrez]
AID - S0006291X03023465 [pii]
AID - 10.1016/j.bbrc.2003.07.019 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 Jan 9;313(2):443-6. doi: 
      10.1016/j.bbrc.2003.07.019.