The Atlantic salmon Z‐DNA binding protein kinase phosphorylates translation initiation factor 2 alpha and constitutes a unique orthologue to the mammalian dsRNA‐activated protein kinase R

• Published in: FEBS Journal
• Main Authors: Bergan, Veronica, Jagus, Rosemary, Lauksund, Silje, Kileng, Øyvind, Robertsen, Børre
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2007
• Subjects: Atlantic salmon
• Online Access: http://dx.doi.org/10.1111/j.1742-4658.2007.06188.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2007.06188.x; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2007.06188.x

The translation initiation factor 2 alpha (eIF2α)‐kinase, dsRNA‐activated protein kinase (PKR), constitutes one of the major antiviral proteins activated by viral infection of vertebrates. PKR is activated by viral double‐stranded RNA and subsequently phosphorylates the α‐subunit of translation initiation factor eIF2. This results in overall down regulation of protein synthesis in the cell and inhibition of viral replication. Fish appear to have a PKR‐like protein that has Z‐DNA binding domains instead of dsRNA binding domains in the regulatory domain, and has thus been termed Z‐DNA binding protein kinase (PKZ). We present the cloning of the Atlantic salmon PKZ cDNA and show its upregulation by interferon in Atlantic salmon TO cells and poly inosinic poly cytodylic acid in head kidney. We also demonstrate that recombinant Atlantic salmon PKZ, expressed in Escherichia coli , phosphorylates eIF2α in vitro . This is the first demonstration that PKZ is able to phosphorylate eIF2α. PKZ activity, as measured by phosphorylation of eIF2α, was increased after addition of Z‐DNA, but not by dsRNA. In addition, we show that wild‐type Atlantic salmon PKZ, but not the kinase defective variant K217R, has a direct inhibitory effect on protein synthesis after transient expression in Chinook salmon embryo cells. Overall, the results support a role for PKZ, like PKR, in host defense against virus infection.