Inhibition of the double‐stranded RNA‐dependent protein kinase PKR by mammalian ribosomes

Previous evidence has shown that the majority of the interferon‐inducible, double‐stranded RNA‐dependent protein kinase PKR is associated with ribosomes in vivo. Here we show that ribosomes are inhibitory for PKR activity since they compete with dsRNA for binding to PKR, inhibit the activation of the protein kinase by dsRNA, and prevent the phosphorylation of the PKR substrate eIF2α. We suggest that ribosomes constitute a reservoir of inactive PKR and that the protein kinase must be displaced from the ribosome by dsRNA in order to become activated.

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