IKKβ is an IRF5 kinase that instigates inflammation

Junyao Ren, Xiang Chen, Zhijian J. Chen

Research output: Contribution to journalArticle

41 Citations (Scopus)

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

Fingerprint

Interferon Regulatory Factors
Phosphotransferases
Inflammation
Serine
Phospho-Specific Antibodies
Cytokines
Toll-Like Receptors
Mass Spectrometry
Protein Isoforms
Transcription Factors
Phosphorylation

Keywords

  • IKK
  • Inflammation
  • IRF5
  • Phosphorylation
  • TLR

ASJC Scopus subject areas

  • General

Cite this

IKKβ is an IRF5 kinase that instigates inflammation. / Ren, Junyao; Chen, Xiang; Chen, Zhijian J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 49, 09.12.2014, p. 17438-17443.

Research output: Contribution to journalArticle

@article{f9f51752b2fa4f8d870fc72f1f8e6c26,
title = "IKKβ 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 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.",
keywords = "IKK, Inflammation, IRF5, Phosphorylation, TLR",
author = "Junyao Ren and Xiang Chen and Chen, {Zhijian J.}",
year = "2014",
month = "12",
day = "9",
doi = "10.1073/pnas.1418516111",
language = "English (US)",
volume = "111",
pages = "17438--17443",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "49",

}

TY - JOUR

T1 - IKKβ is an IRF5 kinase that instigates inflammation

AU - Ren, Junyao

AU - Chen, Xiang

AU - Chen, Zhijian J.

PY - 2014/12/9

Y1 - 2014/12/9

N2 - 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.

AB - 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.

KW - IKK

KW - Inflammation

KW - IRF5

KW - Phosphorylation

KW - TLR

UR - http://www.scopus.com/inward/record.url?scp=84916201016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84916201016&partnerID=8YFLogxK

U2 - 10.1073/pnas.1418516111

DO - 10.1073/pnas.1418516111

M3 - Article

VL - 111

SP - 17438

EP - 17443

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 49

ER -