The kinase activity of PKR represses inflammasome activity

Howard C H Yim, Die Wang, Liang Yu, Christine L. White, Pieter W. Faber, Bryan R G Williams, Anthony J. Sadler

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

The protein kinase R (PKR) functions in the antiviral response by controlling protein translation and inflammatory cell signaling pathways. We generated a transgenic, knock-in mouse in which the endogenous PKR is expressed with a point mutation that ablates its kinase activity. This novel animal allows us to probe the kinase-dependent and-independent functions of PKR. We used this animal together with a previously generated transgenic mouse that is ablated for PKR expression to determine the role of PKR in regulating the activity of the cryopyrin inflammasome. Our data demonstrate that, in contradiction to earlier reports, PKR represses cryopyrin inflammasome activity. We demonstrate that this control is mediated through the established function of PKR to inhibit protein translation of constituents of the inflammasome to prevent initial priming during innate immune signaling. These findings identify an important role for PKR to dampen inflammation during the innate immune response and caution against the previously proposed therapeutic strategy to inhibit PKR to treat inflammation.

Original languageEnglish
Pages (from-to)367-379
Number of pages13
JournalCell Research
Volume26
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016

Keywords

  • inflammasomes
  • inflammation
  • kinase activity
  • protein kinase R
  • protein translation

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