title: Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2alpha kinase homolog.
abstract: Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.
authors.affiliation: Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2716, USA. tdever@box-t.nih.gov
authors.forename: T E
authors.initials: TE
authors.lastname: Dever
authors.forename: R
authors.initials: R
authors.lastname: Sripriya
authors.forename: J R
authors.initials: JR
authors.lastname: McLachlin
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: J R
authors.initials: JR
authors.lastname: Fabian
authors.forename: S R
authors.initials: SR
authors.lastname: Kimball
authors.forename: L K
authors.initials: LK
authors.lastname: Miller
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000201:enzymology*; D002460:Cell Line; D017353:Gene Deletion; D005822:Genetic Vectors; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D018411:Spodoptera; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; C111768:baculovirus PK2; D011494:Protein Kinases; D019892:eIF-2 Kinase