Amino acid signalling upstream of mTOR

Nat Rev Mol Cell Biol. 2013 Mar;14(3):133-9. doi: 10.1038/nrm3522. Epub 2013 Jan 30.

Abstract

Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that is part of mTOR complex 1 (mTORC1), a master regulator that couples amino acid availability to cell growth and autophagy. Multiple cues modulate mTORC1 activity, such as growth factors, stress, energy status and amino acids. Although amino acids are key environmental stimuli, exactly how they are sensed and how they activate mTORC1 is not fully understood. Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Autophagy
  • Cell Proliferation
  • Humans
  • Leucine-tRNA Ligase / metabolism
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Models, Biological
  • Monomeric GTP-Binding Proteins / metabolism
  • Multiprotein Complexes
  • Neuropeptides / metabolism
  • Proteins / metabolism*
  • Ras Homolog Enriched in Brain Protein
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Amino Acids
  • Multiprotein Complexes
  • Neuropeptides
  • Proteins
  • RHEB protein, human
  • Ras Homolog Enriched in Brain Protein
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins
  • Leucine-tRNA Ligase