Amino acid signalling upstream of mTOR
By Jenna L. Jewell, R. Russell, K. Guan. Nature reviews. Molecular cell biology, 2013
868 citations recorded by the source corpus.
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).
Subfields: Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/aec43a5894652f1860cd232801be3838c5236638
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In Epidemiology
In Molecular Biology
- David M. Sabatini
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Citations in the corpus
- mTOR: a pharmacologic target for autophagy regulation. (2015, neutral): “33, 34).”
- Branched Chain Amino Acids: Beyond Nutrition Metabolism (2018, background): “Leucyl-tRNA synthetase (LeuRS), a direct sensor for Leu upstream of mTOR, is a cytoplasmic enzyme and is required for protein synthesis [1].”
- Functional amino acids in nutrition and health (2013, background): “2012), cell signaling (Bazer et al. 2012; Jewell et al. 2013), blood flow (Tan et al.”
- Nutrient sensing and TOR signaling in yeast and mammals (2017, neutral): “Amino acid sufficiency regulates TORC1 via different mechanisms that largely involve the conserved RAG family of small GTPases (for review, see Jewell et al , 2013; Bar-Peled & Sabatini, 2014; Shimobayashi & Hall, 2015; Hatakeyama & De Virgilio, 2016; Powis & De Virgilio, 2016; Fig 1).”
- Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation (2014, neutral): “Amino acids have a crucial role in the activation of the mTOR signaling pathways (Jewell et al., 2013).”
- The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals arginine sufficiency to mTORC1 (2015, background): “RagA and RagB are highly similar and functionally redundant, as are RagC and RagD (1, 6).”
- Regulation of mTORC1 by amino acids (2014, neutral): “Although it was clear for over a decade that amino acids were vital for mTORC1 activation, precisely how this signal functioned remained a mystery (32, 33).”