THE ROLE OF THE DSRNA-ACTIVATED KINASE, PKR, IN SIGNAL-TRANSDUCTION

The double stranded RNA (dsRNA) dependent, interferon (IFN)-induced protein kinase (PKR) plays a dual role in the interferon system. As an IFN-induced enzyme its primary role is in regulating protein synthesis initiation via phosphorylation of initiation factor eLF-2. Recently, manipulation of basal levels of PKR using antisense or gene ablation technologies has identified I kappa B, the inhibitor of transcription factor NF kappa B, as a new substrate for PKR. Phosphorylation of I kappa B by PKR results in the transcriptional activation of NF kappa B-dependent genes including interferon beta (IFN-beta). PKR is also implicated as playing a role at either the translational or transcriptional level in the signal transduction pathways of other cytokines including IL3, PDGF and IFN gamma.