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IKK? is an IRF5 kinase that instigates inflammation.

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 IKK? phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll-like receptors and retinoic acid-inducible gene I-like receptors. IKK? 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 IKK? phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production. Depletion or pharmacologic inhibition of IKK? prevented IRF5 phosphorylation. These results indicate that IKK? is an IRF5 kinase that instigates inflammation.

SUBMITTER: Ren J

PROVIDER: S-EPMC4267374 | biostudies-other | 2014 Dec

REPOSITORIES: biostudies-other

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IKKβ is an IRF5 kinase that instigates inflammation.

Ren Junyao J Chen Xiang X Chen Zhijian J ZJ

Proceedings of the National Academy of Sciences of the United States of America 20141017 49

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 acid-inducible gene I-like receptors. IKKβ phosphorylates mouse IRF5 at specific residues, including serin ...[more]

PMID: 25326420

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