Format

Send to

Choose Destination
Trends Cell Biol. 2014 Jul;24(7):400-6. doi: 10.1016/j.tcb.2014.03.003. Epub 2014 Mar 31.

Regulation of mTORC1 by amino acids.

Author information

1
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Cambridge MA 02142, USA. Electronic address: sabatini@wi.mit.edu.

Abstract

The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes. mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes. Increased understanding of this pathway will not only provide insight into growth control but also into the human pathologies triggered by its deregulation.

KEYWORDS:

GATOR complex; Rag GTPases; Ragulator; amino acid sensing; folliculin

PMID:
24698685
PMCID:
PMC4074565
DOI:
10.1016/j.tcb.2014.03.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center