title: Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation.
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 p38β-PRAK cascade targets Rheb to inhibit mTORC1 activity upon glucose depletion. Here we show the activation of p38β 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 p38β and induces interaction between p38β 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 p38β can target different substrates to either positively or negatively regulate mTORC1 activation when a cell encounters different environmental stresses.
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Wu
authors.forename: Xue-Kun
authors.initials: XK
authors.lastname: Wang
authors.forename: Su-Qin
authors.initials: SQ
authors.lastname: Wu
authors.forename: Jiawei
authors.initials: J
authors.lastname: Lu
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Yan-Hai
authors.initials: YH
authors.lastname: Wang
authors.forename: Huamin
authors.initials: H
authors.lastname: Zhou
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005502:Food; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism*; D046912:Multiprotein Complexes; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D000076223:Regulatory-Associated Protein of mTOR; D012694:Serine / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018053:Arsenites; D002352:Carrier Proteins; D007328:Insulin; D046912:Multiprotein Complexes; D011506:Proteins; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; D012694:Serine; D000841:Anisomycin; D006861:Hydrogen Peroxide; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048290:Mitogen-Activated Protein Kinase 11; C015001:arsenite