The kinase activity of PKR represses inflammasome activity  

作　　者：Howard CH Yim Die Wang Liang Yu Christine L White Pieter W Faber Bryan RG Williams Anthony J Sadler 

机构地区：[1]Centre for Cancer Research, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Victoria 3168, Australia [2]Centrefor lnnate Immunity and lnfectious Diseases, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Victoria 3168, Aus-tralia ~Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia [3]Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia [4]Chicago Ge-nomics Facility, University of Chicago, IL 60637, USA

出　　处：《Cell Research》2016年第3期367-379,共13页细胞研究（英文版）

摘　　要：The protein kinase R （PKR） functions in the antiviral response by controlling protein translation and inflamma- tory 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 pre- viously proposed therapeutic strategy to inhibit PKR to treat inflammation.

关 键 词：INFLAMMATION INFLAMMASOMES protein kinase R kinase activity protein translation 

分 类 号：Q55[生物学—生物化学] Q522