The Double-Stranded RNA Dependent Protein Kinase from Human Cells

Abstract

The protein kinase activity dependent on double-stranded (ds)RNA is enhanced in mouse and human cells following treatment with interferon. This kinase activity is manifested by the phosphorylation of (a) a 65,000–67,000-Mr protein (p65) in mouse cells or a 68,000–72,000-Mr protein (p68) in human cells; (b) a 35,000-Mr protein which is the α -subunit of protein synthesis initiation factor eIF2; and (c) added calf thymus histones (HIIA). This kinase activity is independent of cyclic AMP or cyclic GMP and is markedly stimulated by Mn. It phosphorylates p65 and p68 by their serine and threonine residues. The role of such protein kinase activity is considered to be the phosphorylation of the α -subunit of eIF2, thus mediating inhibition of the initiation of protein synthesis in cell-free system (for references see 1). The phosphorylation of p65 and p68 has been shown during virus infection in mouse and human cells, respectively (2–4). The enhanced phosphorylation of eIF2 has also been reported in interferon-treated cells infected with reovirus or encephalomyocarditis virus (4,5). Recent data in cells infected with adenovirus suggests that the dsRNA-dependent protein kinase plays a decisive role in the control of cellular and viral Referencesprotein synthesis (6).