| First Author | Ren J | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 49 | Pages | 17438-43 |
| PubMed ID | 25326420 | Mgi Jnum | J:216669 |
| Mgi Id | MGI:5609199 | Doi | 10.1073/pnas.1418516111 |
| Citation | Ren J, et al. (2014) IKKbeta is an IRF5 kinase that instigates inflammation. Proc Natl Acad Sci U S A 111(49):17438-43 |
| abstractText | 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 IKKbeta 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. IKKbeta 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 IKKbeta 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 IKKbeta prevented IRF5 phosphorylation. These results indicate that IKKbeta is an IRF5 kinase that instigates inflammation. |
