PMID- 14684179
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  - Regulation of global and specific mRNA translation by oral administration of 
      branched-chain amino acids.
PG  - 423-7
AB  - The importance of branched-chain amino acids as nutrient regulators of protein 
      synthesis in skeletal muscle was recognized more than 20 years ago. Of the 
      branched-chain amino acids, leucine in particular was shown to play a central 
      role in promoting muscle protein synthesis. However, it was only recently that 
      the mechanism(s) involved in the stimulation of protein synthesis by leucine has 
      begun to be defined. Studies performed in our laboratory during the past few 
      years have revealed that oral administration of leucine to fasted rats enhances 
      protein synthesis in association with increased phosphorylation of two proteins 
      downstream of the protein kinase referred to as the mammalian target of rapamycin 
      (mTOR). These proteins, eukaryotic initiation factor eIF4E binding protein 
      (4E-BP)1 and ribosomal protein S6 kinase S6K1, control in part the step in 
      translation initiation involving the binding of mRNA to the 40S ribosomal 
      subunit. In theory the translation of all mRNAs can be regulated through such 
      mechanisms, however, some mRNAs are more sensitive to the changes than others, 
      resulting in modulation of gene expression through altered patterns of 
      translation of specific mRNAs. Moreover, although a basal amount of plasma 
      insulin is required for leucine to enhance signaling downstream of mTOR, the 
      concentration observed in plasma of fasted rats is sufficient to observe maximal 
      changes in phosphorylation of 4E-BP1 and S6K1.
FAU - Kimball, Scot R
AU  - Kimball SR
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, Hershey, PA 17033, USA.
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK13499/DK/NIDDK NIH HHS/United States
GR  - DK15658/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Glucocorticoids)
RN  - 0 (Insulin)
RN  - 0 (Proteins)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Administration, Oral
MH  - Amino Acids, Branched-Chain/*pharmacology/physiology
MH  - Animals
MH  - Gene Expression Regulation/drug effects
MH  - Glucocorticoids/antagonists & inhibitors
MH  - Insulin/metabolism
MH  - Leucine/pharmacology/physiology
MH  - Muscle, Skeletal/metabolism
MH  - Protein Biosynthesis/*drug effects
MH  - Proteins/genetics
MH  - Signal Transduction
MH  - Tissue Distribution
RF  - 22
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 - S0006291X0302343X [pii]
AID - 10.1016/j.bbrc.2003.07.014 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 Jan 9;313(2):423-7. doi: 
      10.1016/j.bbrc.2003.07.014.