Breakpoint cluster region-mediated inflammation is dependent on casein kinase II

Jie Meng, Jing Jing Jiang, Toru Atsumi, Hidenori Bando, Yuko Okuyama, Lavannya Sabharwal, Ikuma Nakagawa, Haruka Higuchi, Mitsutoshi Ota, Momoko Okawara, Ryuichiro Ishitani, Osamu Nureki, Daisuke Higo, Yasunobu Arima, Hideki Ogura, Daisuke Kamimura, Masaaki Murakami

研究成果: Article査読

11 被引用数 (Scopus)

抄録

The breakpoint cluster region (BCR) is known as a kinase and cause of leukemia upon fusing to Abl kinase. In this study, we demonstrate that BCR associated with the a subunit of casein kinase II (CK2a), rather than BCR itself, is required for inflammation development. We found that BCR knockdown inhibited NF-kB activation in vitro and in vivo. Computer simulation, however, suggested that the putative BCR kinase domain has an unstable structure with minimal enzymatic activity. Liquid chromatography-tandem mass spectrometry analysis showed that CK2a associated with BCR. We found the BCR functions are mediated by CK2a. Indeed, CK2a associated with adaptor molecules of TNF-aR and phosphorylated BCR at Y177 to establish a p65 binding site after TNF-a stimulation. Notably, p65 S529 phosphorylation by CK2a creates a p300 binding site and increased p65-mediated transcription followed by inflammation development in vivo. These results suggest that BCR-mediated inflammation is dependent on CK2a, and the BCR-CK2a complex could be a novel therapeutic target for various inflammatory diseases.

本文言語English
ページ(範囲)3111-3119
ページ数9
ジャーナルJournal of Immunology
197
8
DOI
出版ステータスPublished - 2016 10 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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