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

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14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3111-3119
Number of pages9
JournalJournal of Immunology
Issue number8
Publication statusPublished - 2016 Oct 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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