Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-6-30
pubmed:abstractText
The BCAA, leucine, stimulates protein synthesis in skeletal muscle in part through enhanced initiation of mRNA translation. However, understanding how leucine regulates protein synthesis remains elusive. The intent of the present investigation was to examine the effect of leucine, independent of other regulatory agents, on key events in translation initiation in skeletal muscle and to elucidate the extent to which signaling through the mammalian target of rapamycin (mTOR) accounts for the effect of the amino acid on protein synthesis. Hindlimb preparations from postabsorptive rats were perfused with medium containing food-deprived (1X) or superphysiologic (10X) concentrations of leucine with all other amino acids at 1X concentration. Protein synthesis was significantly greater in both gastrocnemius and soleus perfused with 10X compared with 1X leucine. The stimulatory effects of leucine on protein synthesis were unaffected by a specific inhibitor of PI3-kinase (LY 294002). Moreover, signaling through mTOR, as monitored by the phosphorylation status of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) or the 70-kDa ribosomal protein S6 kinase (S6K1), was not further enhanced by 10X compared with 1X leucine. However, binding of eIF4E to eIF4G and eIF4G(Ser-1108) phosphorylation in the eIF4E immunoprecipitate were enhanced as was eIF4G(Ser-1108) phosphorylation in the total tissue extract after perfusion with medium containing 10X leucine. Collectively, these observations illustrate an experimental model whereby leucine in the absence of other regulatory agents stimulates eIF4E. eIF4G assembly and protein synthesis directly in skeletal muscle, possibly by augmenting phosphorylation of eIF4G through a signaling pathway independent of mTOR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3166
pubmed:author
pubmed:issnType
Print
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1704-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation.
pubmed:affiliation
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't