Attenuated Expression of Interferon-induced Protein Kinase PKR in a Simian Cell Devoid of Type I Interferons

The interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase PKR plays a key role in interferon-mediated host defense against viral infection, and is implicated in cellular transformation and apoptosis. We have isolated a cDNA of simian PKR encoding a product with 83% amino acid identity to the human homolog and showed that PKR expression is significantly attenuated in the Vero E6 African green monkey kidney cells devoid of type I interferon genes. A variant form of PKR lacking the exon 12 in the kinase domain is produced in these cells, presumably from an alternatively spliced transcript. Unlike wild type PKR, the variant protein named PKR-DE12 is incapable of auto-phosphorylation and phosphorylation of eIF2-a, indicating that the kinase sub-domains III and IV embedded in exon 12 are indispensable for catalytic function. PKR-DE12 had no dominant negative effect but was weakly phosphorylated in trans by wild type PKR.