The Double-Stranded RNA-Dependent Protein Kinase PKR: Structure and Function

Abstract

This review describes the structure and function of the interferon (IFN)-inducible, double-stranded RNA-activated protein kinase PKR. This protein kinase has been studied extensively in recent years, and a large body of evidence has accumulated concerning its expression, interaction with regulatory RNA and protein molecules, and modes of activation and inhibition. PKR has been shown to play a variety of important roles in the regulation of translation, transcription, and signal transduction pathways through its ability to phosphorylate protein synthesis initiation factor eIF2, I-kappaB (the inhibitor of NF-kappaB), and other substrates. Expression studies involving both the wild-type protein and dominant negative mutants of PKR have established roles for the enzyme in the antiviral effects of IFNs, in the responses of uninfected cells to physiologic stresses, and in cell growth regulation. The possibility that PKR may function as a tumor suppressor and inducer of apoptosis suggests that this IFN-regulated protein kinase may be of central importance to the control of cell proliferation and transformation.