title: Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation.
abstract: mTOR complex 1 (mTORC1) is a multiprotein complex that integrates diverse signals including growth factors, nutrients, and stress to control cell growth. Raptor is an essential component of mTORC1 that functions to recruit specific substrates. Recently, Raptor was suggested to be a key target of regulation of mTORC1. Here, we show that Raptor is phosphorylated by JNK upon osmotic stress. We identified that osmotic stress induces the phosphorylation of Raptor at Ser-696, Thr-706, and Ser-863 using liquid chromatography-tandem mass spectrometry. We found that JNK is responsible for the phosphorylation. The inhibition of JNK abolishes the phosphorylation of Raptor induced by osmotic stress in cells. Furthermore, JNK physically associates with Raptor and phosphorylates Raptor in vitro, implying that JNK is responsible for the phosphorylation of Raptor. Finally, we found that osmotic stress activates mTORC1 kinase activity in a JNK-dependent manner. Our findings suggest that the molecular link between JNK and Raptor is a potential mechanism by which stress regulates the mTORC1 signaling pathway.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Korea.
authors.forename: Dongoh
authors.initials: D
authors.lastname: Kwak
authors.forename: Sunkyu
authors.initials: S
authors.lastname: Choi
authors.forename: Heeyoon
authors.initials: H
authors.lastname: Jeong
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Jang
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyeona
authors.initials: H
authors.lastname: Jeon
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.forename: Jungeun
authors.initials: J
authors.lastname: Noh
authors.forename: Kun
authors.initials: K
authors.lastname: Cho
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Yoo
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure; D010766:Phosphorylation; D034741:RNA, Small Interfering; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D034741:RNA, Small Interfering; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases