Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal kinase (JNK)-mediated raptor protein phosphorylation

Dongoh Kwak, Sunkyu Choi, Heeyoon Jeong, Jin Hyeok Jang, Youngmi Lee, Hyeona Jeon, Mi Nam Lee, Jungeun Noh, Kun Cho, Jong Shin Yoo, Daehee Hwang, Pann Ghill Suh, Sung Ho Ryu

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)18398-18407
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number22
DOIs
Publication statusPublished - 25 May 2012
Externally publishedYes

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Raptors
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Osmotic Pressure
Proteins
Multiprotein Complexes
Liquid chromatography
Cell growth
mechanistic target of rapamycin complex 1
Nutrients
Mass spectrometry
Intercellular Signaling Peptides and Proteins
Tandem Mass Spectrometry
Phosphotransferases
Liquid Chromatography
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal kinase (JNK)-mediated raptor protein phosphorylation. / Kwak, Dongoh; Choi, Sunkyu; Jeong, Heeyoon; Jang, Jin Hyeok; Lee, Youngmi; Jeon, Hyeona; Lee, Mi Nam; Noh, Jungeun; Cho, Kun; Yoo, Jong Shin; Hwang, Daehee; Suh, Pann Ghill; Ryu, Sung Ho.

In: Journal of Biological Chemistry, Vol. 287, No. 22, 25.05.2012, p. 18398-18407.

Research output: Contribution to journalArticle

Kwak, D, Choi, S, Jeong, H, Jang, JH, Lee, Y, Jeon, H, Lee, MN, Noh, J, Cho, K, Yoo, JS, Hwang, D, Suh, PG & Ryu, SH 2012, 'Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal kinase (JNK)-mediated raptor protein phosphorylation', Journal of Biological Chemistry, vol. 287, no. 22, pp. 18398-18407. https://doi.org/10.1074/jbc.M111.326538
Kwak, Dongoh ; Choi, Sunkyu ; Jeong, Heeyoon ; Jang, Jin Hyeok ; Lee, Youngmi ; Jeon, Hyeona ; Lee, Mi Nam ; Noh, Jungeun ; Cho, Kun ; Yoo, Jong Shin ; Hwang, Daehee ; Suh, Pann Ghill ; Ryu, Sung Ho. / Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal kinase (JNK)-mediated raptor protein phosphorylation. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 22. pp. 18398-18407.
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