Key mediators of intracellular amino acids signaling to mTORC1 activation

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Cell Proliferation
  • Class III Phosphatidylinositol 3-Kinases / genetics
  • Class III Phosphatidylinositol 3-Kinases / metabolism
  • Endosomes / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Lysosomes / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Protein Transport
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Ras Homolog Enriched in Brain Protein
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Amino Acids
  • Multiprotein Complexes
  • Neuropeptides
  • RHEB protein, human
  • Ras Homolog Enriched in Brain Protein
  • TOR Serine-Threonine Kinases
  • Class III Phosphatidylinositol 3-Kinases
  • MAP4K3 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • Protein-Serine-Threonine Kinases
  • Monomeric GTP-Binding Proteins