Role of the RNA-dependent protein kinase in the regulated expression of genes in transfected cells

Abstract

The RNA-dependent P1/eIF-2 alpha protein kinase is a highly specific protein-serine/threonine kinase that catalyzes the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF-2. The kinase plays a central role in translational control. The activity of the kinase is regulated by a variety of naturally occurring effector RNAs which bind to the regulatory domain of the enzyme. Certain RNAs are able to activate the eIF-2 alpha kinase activity inherent within protein P1, a process which involves an autophosphorylation of protein P1, whereas other RNAs are able to antagonize the activation process. Translational repression mediated by the kinase may also be disrupted by RNA binding proteins that sequester activator double-stranded RNAs and by site-directed mutants and homologs of the eIF-2 alpha translation factor substrate. The P1/eIF-2 alpha protein kinase is an important regulator of the translation of plasmid-derived mRNAs in transfected eukaryotic cells.