1. Leucine stimulates HGF production by hepatic stellate cells through mTOR pathway.
- Author
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Tomiya T, Nishikawa T, Inoue Y, Ohtomo N, Ikeda H, Tejima K, Watanabe N, Tanoue Y, Omata M, and Fujiwara K
- Subjects
- Animals, Carrier Proteins metabolism, Cell Line, Enzyme Activation, Intracellular Signaling Peptides and Proteins, Leucine pharmacology, Liver cytology, Liver metabolism, Phosphoproteins metabolism, Phosphorylation, Rats, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Signal Transduction, TOR Serine-Threonine Kinases, Hepatocyte Growth Factor biosynthesis, Leucine physiology, Protein Kinases metabolism
- Abstract
Branched chain amino acids modulate various cellular functions in addition to providing substrates for the production of proteins. We examined the mechanism underlying the stimulation by leucine of hepatocyte growth factor (HGF) production by hepatic stellate cells. Both p70 S6 kinase activity and phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were up-regulated rapidly after leucine treatment of a rat hepatic stellate cell clone. No such activation was observed following treatment with valine or isoleucine. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suppressed leucine-induced activation of p70 S6 kinase and 4E-BP1 and negated the stimulatory effect of leucine on HGF production. An mTOR-dependent signaling pathway mediates the stimulatory effect of leucine on the production of HGF by hepatic stellate cells.
- Published
- 2007
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