An interferon-inducible, RNA-dependent protein serine/threonine kinase (PKR) has been described. PKR in earlier literature is variously known as DAI, dsJ, PI kinase, p65, p67 or TIK for the mouse kinase; and p68 or p69 for the human kinase. The PKR kinase substrate is the alpha subunit of protein synthesis initiation factor eIF-2. Phosphorylation of eIF-2alpha on serine-51 results in inhibition of translation. Molecular cDNA clones have been isolated from both human and mouse cells. The serine/threonine kinase catalytic domains map to the carboxy terminal half of the protein while the RNA-binding domains are located in the amino terminal region. Three kinds of regulation of PKR enzymatic activity have been described.