PMID- 16365087
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20230216
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 136
IP  - 1 Suppl
DP  - 2006 Jan
TI  - Signaling pathways and molecular mechanisms through which branched-chain amino 
      acids mediate translational control of protein synthesis.
PG  - 227S-31S
LID - 10.1093/jn/136.1.227S [doi]
AB  - BCAAs stimulate protein synthesis in in vitro preparations of skeletal muscle. 
      Likewise, the stimulation of protein synthesis in skeletal muscle produced by 
      intake of a mixed meal is due largely to BCAAs. Of the three BCAAs, leucine is 
      the one primarily responsible for the stimulation of protein synthesis under 
      these circumstances. The stimulatory effect of leucine on protein synthesis is 
      mediated through upregulation of the initiation of mRNA translation. A number of 
      mechanisms, including phosphorylation of ribosomal protein S6 Kinase, eukaryotic 
      initiation factor (eIF)4E binding protein-1, and eIF4G, contribute to the effect 
      of leucine on translation initiation. These mechanisms not only promote global 
      translation of mRNA but also contribute to processes that mediate discrimination 
      in the selection of mRNA for translation. A key component in a signaling pathway 
      controlling these phosphorylation-induced mechanisms is the protein kinase, 
      termed the mammalian target of rapamycin (mTOR). The activity of mTOR toward 
      downstream targets is controlled in part through its interaction with the 
      regulatory-associated protein of mTOR (known as raptor) and the G protein 
      beta-subunit-like protein. Signaling through mTOR is also controlled by upstream 
      members of the pathway such as the Ras homolog enriched in brain (Rheb), a GTPase 
      that activates mTOR, and tuberin (also known as TSC2), a GTPase-activating 
      protein, which, with its binding partner hamartin (also known as TSC1), acts to 
      repress mTOR. Candidates for mediating the action of leucine to stimulate 
      signaling through the mTOR pathway include TSC2, Rheb, and raptor. The current 
      state of our understanding of how leucine acts on these signaling pathways and 
      molecular mechanisms to stimulate protein synthesis in skeletal muscle is 
      summarized in this article.
FAU - Kimball, Scot R
AU  - Kimball SR
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, PA, USA. jjefferson@psu.edu
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK-13499/DK/NIDDK NIH HHS/United States
GR  - DK-15658/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Insulin)
RN  - 0 (Neuropeptides)
RN  - 0 (RHEB protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Insulin/physiology
MH  - Leucine/*pharmacology
MH  - Monomeric GTP-Binding Proteins/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Neuropeptides/metabolism
MH  - Protein Biosynthesis/*drug effects
MH  - Protein Kinases/physiology
MH  - RNA, Messenger/analysis
MH  - Ras Homolog Enriched in Brain Protein
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
RF  - 43
EDAT- 2005/12/21 09:00
MHDA- 2006/03/03 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - S0022-3166(22)08038-5 [pii]
AID - 10.1093/jn/136.1.227S [doi]
PST - ppublish
SO  - J Nutr. 2006 Jan;136(1 Suppl):227S-31S. doi: 10.1093/jn/136.1.227S.