RSK2 is required for TRAF6 phosphorylation-mediated colon inflammation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-03-22

AUTHORS

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

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. More... »

PAGES

3501-3513

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-018-0167-6

DOI

http://dx.doi.org/10.1038/s41388-018-0167-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101632771

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29563609


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380 The Hormel Institute, University of Minnesota, 801 16th Ave NE, 55912, Austin, MN, USA
381 rdf:type schema:Organization
 




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