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Amino Acids. 2015 May;47(5):857-67. doi: 10.1007/s00726-015-1937-x. Epub 2015 Feb 21.

Key mediators of intracellular amino acids signaling to mTORC1 activation.

Author information

1
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.

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.

PMID:
25701492
DOI:
10.1007/s00726-015-1937-x
[Indexed for MEDLINE]

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