title: Key mediators of intracellular amino acids signaling to mTORC1 activation.
abstract: Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.
authors.affiliation: Chinese Academy of Science, Institute of Subtropical Agriculture, Research Center for Healthy Breeding Livestock and Poultry, Hunan Engineering and Research Center for Animal and Poultry Science, Key Laboratory of Agroecology in Subtropical Region, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Changsha, Hunan, 410125, People's Republic of China.
authors.forename: Yehui
authors.initials: Y
authors.lastname: Duan
authors.forename: Fengna
authors.initials: F
authors.lastname: Li
authors.forename: Kunrong
authors.initials: K
authors.lastname: Tan
authors.forename: Hongnan
authors.initials: H
authors.lastname: Liu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Kong
authors.forename: Yulong
authors.initials: Y
authors.lastname: Tang
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D058546:Class III Phosphatidylinositol 3-Kinases; C543044:MAP4K3 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins