Activation of protein kinase PKR requires dimerization-induced cis-phosphorylation within the activation loop.

ABSTRACT: Protein kinase R (PKR) functions in a plethora of cellular processes, including viral and cellular stress responses, by phosphorylating the translation initiation factor eIF2α. The minimum requirements for PKR function are homodimerization of its kinase and RNA-binding domains, and autophosphorylation at the residue Thr-446 in a flexible loop called the activation loop. We investigated the interdependence between dimerization and Thr-446 autophosphorylation using the yeast Saccharomyces cerevisiae model system. We showed that an engineered PKR that bypassed the need for Thr-446 autophosphorylation (PKR(T446∼P)-bypass mutant) could function without a key residue (Asp-266 or Tyr-323) that is essential for PKR dimerization, suggesting that dimerization precedes and stimulates activation loop

SUBMITTER: Dey M 

PROVIDER: S-EPMC3937647 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature