The Role of Protein Kinase R in the Interferon Response

The effects of interferons (IFNs) are mediated through the induction of around 2,000 IFN-stimulated gene (ISG) products. However, the majority of these ISGs do not directly instigate IFN-mediated states, such as the defining resistance to viral infection. Rather, most ISGs encode cell signaling molecules that enhance the responsiveness to pathogens, and systemically disseminate signals from localized sites of infection. Relatively few IFN effector proteins have been well characterized. The protein kinase R (PKR) is one of the first and best characterized of these effector molecules. PKR mediates responses via phosphorylation of protein substrates and promotes signal transduction pathways to maintain homeostasis, mediate immune responses, and, upon sustained activation, promote apoptosis. As a number of reviews have dealt with PKR-dependent resistance to virus, this review will cover broader roles ascribed to PKR and the mechanism(s) by which PKR exerts its effects.