RSK2 is required for TRAF6 phosphorylation-mediated colon inflammation

Ke Yao, Sung Young Lee, Cong Peng, Do Young Lim, Hiroyuki Yamamoto, Joohyun Ryu, Tae Gyu Lim, Hanyong Chen, Guoguo Jin, Zhenjiang Zhao, Yaping Han, Wei Ya Ma, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Inflammation is a complex biological host reaction to tissue damage, infection and trauma. Extensive study of the inflammatory response has led to the identification of several protein kinases that are essential for signaling and could be potential therapeutic targets. The RSK family of kinases has multiple cellular functions. In our study, we found that RSK2 is a mediator for inflammation signaling and interacts with TRAF6. In vitro kinase assay results indicated that RSK2 strongly phosphorylates TRAF6 at serines 46, 47 and 48. Ectopic overexpression of TRAF6 or knocking down RSK2 expression confirmed that RSK2 is a positive regulator of TRAF6 K63 ubiquitination. TRAF6 is also required for RSK2 ubiquitination. TRAF6 bridges the TNF receptor superfamily and intracellular signaling for the induction of proinflammatory cytokines. We developed a colon inflammation model using RSK2 wild type (WT) and knockout (KO) mice. As expected, F4/80 and CD3 infiltration were significantly upregulated in WT mice compared to RSK2 KO mice. Furthermore, inflammation signaling, including Ikkα/β, p38 and JNKs, was dramatically upregulated in WT mice. Colon tissue immunoprecipitation results further confirmed that TRAF6 K63 ubiquitination was lower in RSK2 KO mice. Overall, these results indicate that phosphorylation of TRAF6 (S46, 47, 48) by RSK2 is required for TRAF6 K63 ubiquitination and inflammation signaling.

Original languageEnglish (US)
Pages (from-to)3501-3513
Number of pages13
JournalOncogene
Volume37
Issue number26
DOIs
StatePublished - Jun 1 2018

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TNF Receptor-Associated Factor 6
Colon
Phosphorylation
Inflammation
Ubiquitination
Knockout Mice
Phosphotransferases
Inflammation Mediators
Tumor Necrosis Factor Receptors
Immunoprecipitation
Protein Kinases
Serine
Cytokines

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

RSK2 is required for TRAF6 phosphorylation-mediated colon inflammation. / Yao, Ke; Lee, Sung Young; Peng, Cong; Lim, Do Young; Yamamoto, Hiroyuki; Ryu, Joohyun; Lim, Tae Gyu; Chen, Hanyong; Jin, Guoguo; Zhao, Zhenjiang; Han, Yaping; Ma, Wei Ya; Bode, Ann M.; Dong, Zigang.

In: Oncogene, Vol. 37, No. 26, 01.06.2018, p. 3501-3513.

Research output: Contribution to journalArticle

Yao, K, Lee, SY, Peng, C, Lim, DY, Yamamoto, H, Ryu, J, Lim, TG, Chen, H, Jin, G, Zhao, Z, Han, Y, Ma, WY, Bode, AM & Dong, Z 2018, 'RSK2 is required for TRAF6 phosphorylation-mediated colon inflammation', Oncogene, vol. 37, no. 26, pp. 3501-3513. https://doi.org/10.1038/s41388-018-0167-6
Yao, Ke ; Lee, Sung Young ; Peng, Cong ; Lim, Do Young ; Yamamoto, Hiroyuki ; Ryu, Joohyun ; Lim, Tae Gyu ; Chen, Hanyong ; Jin, Guoguo ; Zhao, Zhenjiang ; Han, Yaping ; Ma, Wei Ya ; Bode, Ann M. ; Dong, Zigang. / RSK2 is required for TRAF6 phosphorylation-mediated colon inflammation. In: Oncogene. 2018 ; Vol. 37, No. 26. pp. 3501-3513.
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