Metabolism. Differential regulation of mTORC1 by leucine and glutamine.
Science
; 347(6218): 194-8, 2015 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-25567907
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Monoméricas de Ligação ao GTP
/
Complexos Multiproteicos
/
Serina-Treonina Quinases TOR
/
Glutamina
/
Leucina
/
Lisossomos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos