A heat-sensitive inhibitor in poliovirus-infected cells which selectively blocks phosphorylation of the alpha subunit of eucaryotic initiation factor 2 by the double-stranded RNA-activated protein kinase.
We partially purified an inhibitor from poliovirus-infected HeLa cells which specifically blocked phosphorylation of the alpha subunit of eucaryotic initiation factor 2 by the double-stranded RNA-activated protein kinase. The inhibitory activity eluted from a sizing column with an approximate molecular weight of 80,000 to 100,000 and was sensitive to heat, suggesting a protein nature for the inhibitor. No specific virus-encoded protein purified with the inhibitor. The inhibition of phosphorylation of the alpha subunit of eucaryotic initiation factor 2 was not due to a protein phosphatase associated with the inhibitor. The inhibitor did not seem to prevent phosphorylation of the double-stranded RNA-activated protein kinase but inhibited the phosphorylation of the alpha subunit of eucaryotic initiation factor 2 by the activated kinase. Double-stranded RNA-induced inhibition of in vitro protein synthesis in reticulocyte lysates could be prevented by the addition of the partially purified inhibitor during preincubation of lysate with double-stranded RNA.
Ransone
L J
LJ
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024.
Dasgupta
A
A
D001345:Autoradiography; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D015852:Eukaryotic Initiation Factor-2; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D017955:Poliovirus / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014764:Viral Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D012330:RNA, Double-Stranded; D014764:Viral Proteins; D011494:Protein Kinases; D019892:eIF-2 Kinase