TY - JOUR
T1 - Protein kinase R and the inflammasome
AU - Yim, Howard Chi Ho
AU - Williams, Bryan Raymond George
PY - 2014
Y1 - 2014
N2 - Protein kinase R (PKR) was first identified as a mediator of the double-stranded RNA (dsRNA)-mediated inhibition of protein synthesis in extracts from interferon-treated cells. In a physiological context, viral replication results in production of dsRNA, activation of PKR by autophosphorylation, and phosphorylation of the protein synthesis initiation factor eIF2alpha. Subsequent biochemical, structural, and genetic analyses have identified the dsRNA and kinase domain structure of PKR, and shown that its deletion from the germline of mice results in impaired resistance to infection by many different viruses. These studies have also opened up roles for PKR in different signaling pathways, the most recent being regulation of the inflammasome. Here we review evidence for this newly ascribed function for PKR and discuss roles in inflammasome regulation and associated diseases.
AB - Protein kinase R (PKR) was first identified as a mediator of the double-stranded RNA (dsRNA)-mediated inhibition of protein synthesis in extracts from interferon-treated cells. In a physiological context, viral replication results in production of dsRNA, activation of PKR by autophosphorylation, and phosphorylation of the protein synthesis initiation factor eIF2alpha. Subsequent biochemical, structural, and genetic analyses have identified the dsRNA and kinase domain structure of PKR, and shown that its deletion from the germline of mice results in impaired resistance to infection by many different viruses. These studies have also opened up roles for PKR in different signaling pathways, the most recent being regulation of the inflammasome. Here we review evidence for this newly ascribed function for PKR and discuss roles in inflammasome regulation and associated diseases.
UR - http://online.liebertpub.com/doi/pdf/10.1089/jir.2014.0008
U2 - 10.1089/jir.2014.0008
DO - 10.1089/jir.2014.0008
M3 - Article
VL - 34
SP - 447
EP - 454
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 6
ER -