Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2α RNA-dependent protein kinase
Copyright policy )Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2α RNA-dependent protein kinase
Phosphorylation of the α-subunit of translation eukaryotic initiation factor-2 (eIF2) leads to the inhibition of protein synthesis in response to diverse conditions of stress. Serine/threonine RNA-dependent protein kinase (PKR) is an eIF2α kinase family member induced by type I IFN and activated in response to dsRNA or virus infection. Herein, we demonstrate that human PKR is a dual specificity kinase phosphorylated at Y101, Y162 and Y293 in vitro and in vivo . Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2α phosphorylation of PKR. Biologically, tyrosine phosphorylation of PKR mediates the antiviral and antiproliferative properties of the kinase through its ability to control translation. Our data demonstrate an important role of tyrosine phosphorylation in biochemical and biological processes caused or mediated by the activation of the eIF2α kinase PKR.
- McGill University Canada
- Memorial Sloan Kettering Cancer Center United States
- Jewish General Hospital Canada
Mice, Knockout, Immunoblotting, Colony-Forming Units Assay, Enzyme Activation, Mice, eIF-2 Kinase, Protein Biosynthesis, Mutation, Animals, Humans, Immunoprecipitation, Tyrosine, Phosphorylation, Cells, Cultured, Cell Proliferation
Mice, Knockout, Immunoblotting, Colony-Forming Units Assay, Enzyme Activation, Mice, eIF-2 Kinase, Protein Biosynthesis, Mutation, Animals, Humans, Immunoprecipitation, Tyrosine, Phosphorylation, Cells, Cultured, Cell Proliferation
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