Amino acid signalling upstream of mTOR.
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).
Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Jenna L
JL
Jewell
Ryan C
RC
Russell
Kun-Liang
KL
Guan
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D049109:Cell Proliferation; D006801:Humans; D007935:Leucine-tRNA Ligase / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D046912:Multiprotein Complexes; D009479:Neuropeptides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D000596:Amino Acids; D046912:Multiprotein Complexes; D009479:Neuropeptides; D011506:Proteins; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins; D007935:Leucine-tRNA Ligase