PMID- 17466941
OWN - NLM
STAT- MEDLINE
DCOM- 20070727
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 358
IP  - 1
DP  - 2007 Jun 22
TI  - Leucine stimulates HGF production by hepatic stellate cells through mTOR pathway.
PG  - 176-80
AB  - 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.
FAU - Tomiya, Tomoaki
AU  - Tomiya T
AD  - Department of Gastroenterology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 
      Tokyo 113-8655, Japan. tomiya-1im@h.u-tokyo.ac.jp
FAU - Nishikawa, Takako
AU  - Nishikawa T
FAU - Inoue, Yukiko
AU  - Inoue Y
FAU - Ohtomo, Natsuko
AU  - Ohtomo N
FAU - Ikeda, Hitoshi
AU  - Ikeda H
FAU - Tejima, Kazuaki
AU  - Tejima K
FAU - Watanabe, Naoko
AU  - Watanabe N
FAU - Tanoue, Yasushi
AU  - Tanoue Y
FAU - Omata, Masao
AU  - Omata M
FAU - Fujiwara, Kenji
AU  - Fujiwara K
LA  - eng
PT  - Journal Article
DEP - 20070423
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Cell Line
MH  - Enzyme Activation
MH  - Hepatocyte Growth Factor/*biosynthesis
MH  - Intracellular Signaling Peptides and Proteins
MH  - Leucine/pharmacology/*physiology
MH  - Liver/cytology/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/05/01 09:00
MHDA- 2007/07/28 09:00
CRDT- 2007/05/01 09:00
PHST- 2007/04/11 00:00 [received]
PHST- 2007/04/16 00:00 [accepted]
PHST- 2007/05/01 09:00 [pubmed]
PHST- 2007/07/28 09:00 [medline]
PHST- 2007/05/01 09:00 [entrez]
AID - S0006-291X(07)00822-4 [pii]
AID - 10.1016/j.bbrc.2007.04.093 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2007 Jun 22;358(1):176-80. doi: 
      10.1016/j.bbrc.2007.04.093. Epub 2007 Apr 23.