IKKβ is an IRF5 kinase that instigates inflammation

Junyao Ren, Xiang Chen, Zhijian J. Chen

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The transcription factor interferon regulatory factor 5 (IRF5) is essential for the induction of inflammatory cytokines, but the mechanism by which IRF5 is activated is not well understood. Here we present evidence that the kinase IKKβ phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll-like receptors and retinoic acidinducible gene I-like receptors. IKKβ phosphorylates mouse IRF5 at specific residues, including serine 445 (S446 in human IRF5 isoform 1), as evidenced by mass spectrometry analysis and detection with a phosphospecific antibody. Recombinant IKKβ phosphorylated IRF5 at Ser-445 in vitro, and a pointmutation of this serine abolished IRF5 activation and cytokine production. Depletion or pharmacologic inhibition of IKKβ prevented IRF5 phosphorylation. These results indicate that IKKβ is an IRF5 kinase that instigates inflammation.

Original languageEnglish (US)
Pages (from-to)17438-17443
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number49
DOIs
StatePublished - Dec 9 2014

Keywords

  • IKK
  • IRF5
  • Inflammation
  • Phosphorylation
  • TLR

ASJC Scopus subject areas

  • General

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