Figure 6. Mechanism of action of PKR.

Protein kinase R (PKR) is constitutively expressed, and is also induced by type I interferons (IFNs) under the control of a kinase conserved sequence (KCS) and IFN-stimulated response element (ISRE) in the promoter of PKR. The kinase accumulates in the nucleus and cytoplasm as an inactive monomer, which is activated directly by viral RNAs, and by several other ligands, such as ceramide or the protein activator PACT (protein activator of the IFN-inducible protein kinase). Following activation, PKR monomers are phosphorylated and dimerize to form the active enzyme. Activated PKR regulates several cell signalling pathways through mechanisms that have not been fully explained, but a crucial function of PKR in viral defence is the inhibition of translation by phosphorylation of eukaryotic translation initiation factor 2α (EIF2α).