| First Author | Jewell JL | Year | 2015 |
| Journal | Science | Volume | 347 |
| Issue | 6218 | Pages | 194-8 |
| PubMed ID | 25567907 | Mgi Jnum | J:217369 |
| Mgi Id | MGI:5613816 | Doi | 10.1126/science.1259472 |
| Citation | Jewell JL, et al. (2015) Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science 347(6218):194-8 |
| abstractText | The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H(+)-adenosine triphosphatase (v-ATPase). We report that leucine and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms, respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation factor-1 GTPase to be required for mTORC1 activation and lysosomal localization by glutamine. Our results uncover a signaling cascade to mTORC1 activation independent of the Rag GTPases and suggest that mTORC1 is differentially regulated by specific amino acids. |
