Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2alpha kinase homolog

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....

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-04, Vol.95 (8), p.4164
Main Authors: Dever, T E, Sripriya, R, McLachlin, J R, Lu, J, Fabian, J R, Kimball, S R, Miller, L K
Format: Article
Language:English
Subjects:
Animals
Baculoviridae - enzymology
Biochemistry
Cell Line
Cellular biology
eIF-2 Kinase - biosynthesis
eIF-2 Kinase - metabolism
Gene Deletion
Genetic Vectors
Guanine Nucleotide Exchange Factors
Humans
Phosphorylation
Polymerase Chain Reaction
Protein Biosynthesis
Protein Kinases - genetics
Protein Kinases - metabolism
Proteins
Proteins - metabolism
Recombinant Proteins - metabolism
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Spodoptera
Transfection
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Replication
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.8.4164