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Publication : The kinase activity of PKR represses inflammasome activity.

First Author  Yim HC Year  2016
Journal  Cell Res Volume  26
Issue  3 Pages  367-79
PubMed ID  26794869 Mgi Jnum  J:240799
Mgi Id  MGI:5896452 Doi  10.1038/cr.2016.11
Citation  Yim HC, et al. (2016) The kinase activity of PKR represses inflammasome activity. Cell Res 26(3):367-79
abstractText  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.
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