Nature Communications (Nov 2021)

Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation

  • Grigory Ryzhakov,
  • Hannah Almuttaqi,
  • Alastair L. Corbin,
  • Dorothée L. Berthold,
  • Tariq Khoyratty,
  • Hayley L. Eames,
  • Samuel Bullers,
  • Claire Pearson,
  • Zhichao Ai,
  • Kristina Zec,
  • Sarah Bonham,
  • Roman Fischer,
  • Luke Jostins-Dean,
  • Simon P. L. Travis,
  • Benedikt M. Kessler,
  • Irina A. Udalova

DOI
https://doi.org/10.1038/s41467-021-27038-5
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

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The transcription factor, IRF5, has been implicated in the regulation of inflammation, but how IRF5 protein is activated is still unclear. Here the authors use inhibitor library screening, biochemical analyses and in vivo/ex vivo data to show that a protein tyrosine kinase, Pyk2, may be key for the activation of IRF5 in macrophages and inflammatory responses in the gut.