INHIBITION OF THE DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE PKR BYMAMMALIAN RIBOSOMES

Previous evidence has shown that the majority of the interferon-induci ble, double-stranded RNA-dependent protein kinase PKR is associated wi th ribosomes in vivo. Here we show that ribosomes are inhibitory for P KR activity since they compete with dsRNA for binding to PKR, inhibit the activation of the protein kinase by dsRNA, and prevent the phospho rylation of the PKR substrate eIF2 alpha. We suggest that ribosormes c onstitute a reservoir of inactive PKR and that the protein kinase must be displaced from the ribosome by dsRNA in order to become activated. (C) 1998 Federation of European Biochemical Societies.