Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation.
J Biol Chem
; 286(36): 31501-11, 2011 Sep 09.
Article
en En
| MEDLINE
| ID: mdl-21757713
ABSTRACT
Cell growth is influenced by environmental stress. Mammalian target of rapamycin (mTOR), the central regulator of cell growth, can be positively or negatively regulated by various stresses through different mechanisms. The p38 MAP kinase pathway is essential in cellular stress responses. Activation of MK2, a downstream kinase of p38α, enhances mTOR complex 1 (mTORC1) activity by preventing TSC2 from inhibiting mTOR activation. The p38ß-PRAK cascade targets Rheb to inhibit mTORC1 activity upon glucose depletion. Here we show the activation of p38ß participates in activation of mTOR complex 1 (mTORC1) induced by arsenite but not insulin, nutrients, anisomycin, or H(2)O(2). Arsenite treatment of cells activates p38ß and induces interaction between p38ß and Raptor, a regulatory component of mTORC1, resulting in phosphorylation of Raptor on Ser(863) and Ser(771). The phosphorylation of Raptor on these sites enhances mTORC1 activity, and contributes largely to arsenite-induced mTORC1 activation. Our results shown here and in previous work demonstrate that the p38 pathway can regulate different components of the mTORC1 pathway, and that p38ß can target different substrates to either positively or negatively regulate mTORC1 activation when a cell encounters different environmental stresses.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Proteínas Portadoras
/
Arsenitos
/
Proteína Quinasa 11 Activada por Mitógenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2011
Tipo del documento:
Article
País de afiliación:
China