INTERFERON-ALPHA INDUCES PROTEIN-KINASE C-EPSILON (PKC-EPSILON) GENE-EXPRESSION AND A 4.7-KB PKC-EPSILON-RELATED TRANSCRIPT

Protein kinases play key roles in the induction by human interferon al pha (IFN-alpha) of specific gene expression and biological activity in various human cell lines. We now report that IFN-alpha increased the 7-kb transcript for the epsilon isotype of protein kinase C (PKC-epsil on) and the cellular content of PKC-epsilon 24 and 48 hr after IFN-alp ha addition (a 2-fold and 6-fold increase, respectively). Furthermore, IFN-alpha markedly induced a 4.7-kb transcript that hybridized to a P KC-epsilon-specific, but not to a PKC-eta-specific, cDNA probe. The in duction of the 4.7-kb PKC-epsilon-related mRNA by IFN-alpha had the fo llowing properties reported for the classical IFN-alpha-stimulated gen es: rapid kinetics of induction, high maintained levels in IFN-alpha-s ensitive but not in IFN-alpha-resistant cell lines, protein synthesis- independent induction, and high sensitivity to inhibitors of protein t yrosine kinase activity. These results show that the regulation of gen e expression by IFN-alpha include not only the classical EFN-alpha-sti mulated genes but also the coordinated regulation of two PKC-epsilon-r elated transcripts that appeared to be highly relevant to the biologic al actions of IFN-alpha.