Volume 26, No 3, Mar 2016
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 26 Issue 3, March 2016: 367-379
ORIGINAL ARTICLES
The kinase activity of PKR represses inflammasome activity
Howard CH Yim1,3, Die Wang1,3, Liang Yu2,3, Christine L White1,3, Pieter W Faber4, Bryan RG Williams1,3 and Anthony J Sadler1,3
1Centre for Cancer Research, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Victoria 3168, Australia
2Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Victoria 3168, Australia
3Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia
4Chicago Genomics Facility, University of Chicago, IL 60637, USA
Correspondence: Anthony J Sadler, Tel: +61 3 8572 2722; Fax: +61 3 9594 7167(anthony.sadler@hudson.org.au)
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.
10.1038/cr.2016.11
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