THE INTERFERON-INDUCIBLE PROTEIN-KINASE PKR MODULATES THE TRANSCRIPTIONAL ACTIVATION OF IMMUNOGLOBULIN-KAPPA GENE

PKR is an interferon (IFN)-induced serine/threonine protein kinase tha t regulates protein synthesis through phosphorylation of eukaryotic tr anslation initiation factor-2 (eIF-2). In addition to its demonstrated role in translational control, recent findings suggest that PKR plays an important role in regulation of gene transcription, as PKR phospho rylates I kappa B alpha upon double-stranded RNA treatment resulting i n activation of NF-kappa B DNA binding in vitro (Kumar, A., Haque, J., Lacoste, J., Hiscott, J., and Williams, B. R. G. (1994) Proc. Natl. A cad. Sci. U.S.A. 91, 6288-6292). To further investigate the role of PK R in transcriptional signaling, we expressed the wild type human PKR a nd a catalytically inactive dominant negative PKR mutant in the murine pre-B lymphoma 70Z/3 cells. Here, we report that expression of wild t ype PKR had no effect on kappa-chain transcriptional activation induce d by lipopolysaccharide or IFN-gamma. However, expression of the domin ant negative PKR mutant inhibited kappa gene transcription independent ly of NF-kappa B activation. Phosphorylation of eIF-2 alpha was not in creased by lipopolysaccharide or IFN-gamma, suggesting that PKR mediat es kappa gene transcriptional activation without affecting protein syn thesis. Our findings further support a transcriptional role for PKR an d demonstrate that there are at least two distinct PKR-mediated signal transduction pathways to the transcriptional machinery depending on c ell type and stimuli, NF-kappa B-dependent and NF-kappa B-independent.