Tomiya Tomoaki, Nishikawa Takako, Inoue Yukiko, Ohtomo Natsuko, Ikeda Hitoshi, Tejima Kazuaki, Watanabe Naoko, Tanoue Yasushi, Omata Masao, Fujiwara Kenji
Department of Gastroenterology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan.
Biochem Biophys Res Commun. 2007 Jun 22;358(1):176-80. doi: 10.1016/j.bbrc.2007.04.093. Epub 2007 Apr 23.
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.
支链氨基酸除了为蛋白质合成提供底物外，还能调节多种细胞功能。我们研究了亮氨酸刺激肝星状细胞产生肝细胞生长因子（HGF）的潜在机制。用亮氨酸处理大鼠肝星状细胞克隆后，p70 S6激酶活性和真核起始因子4E结合蛋白1（4E-BP1）的磷酸化迅速上调。用缬氨酸或异亮氨酸处理后未观察到这种激活。雷帕霉素是哺乳动物雷帕霉素靶蛋白（mTOR）的抑制剂，它抑制了亮氨酸诱导的p70 S6激酶和4E-BP1的激活，并消除了亮氨酸对HGF产生的刺激作用。一条mTOR依赖的信号通路介导了亮氨酸对肝星状细胞产生HGF的刺激作用。
