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Amino acid signalling upstream of mTOR

Nature Reviews Molecular Cell Biology volume 14, pages 133–139 (2013)Cite this article

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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).

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Figure 1: The mTORC1 signalling pathway.
Figure 2: Amino acid-induced mTORC1 activation in mammals and yeast.
Figure 3: mTORC1 activation at the lysosome.

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Acknowledgements

The authors are grateful to their colleague R. Gong and the rest of the Guan laboratory for valuable discussions and insightful comments. In addition, the authors would like to thank V. S. Tagliabracci for critical reading of this manuscript. The authors would like to apologize to their colleagues whose work could not be cited owing to space limitations. The work in the Guan laboratory was supported by a National Institutes of Health (NIH) grant (CA108941) and a grant from the Department of Defense (W81XWH-09-1-0279) to K.L.G. J.L.J is supported by a grant from the National Cancer Institute (T32CA121938), and R.C.R is supported by a grant from the Canadian Institute of Health Research (CIHR).

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  1. Ryan C. Russell and Kun-Liang Guan are at the Department of Pharmacology and Moores Cancer Center, Jenna L. Jewell, University of California, San Diego, La Jolla, California 92093, USA.,

    Jenna L. Jewell, Ryan C. Russell & Kun-Liang Guan

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Jewell, J., Russell, R. & Guan, KL. Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 14, 133–139 (2013). https://doi.org/10.1038/nrm3522

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