Inhibitor of interferon-induced double-stranded RNA-dependent protein kinase and its relevance to alteration of cellular protein kinase activity level in response to external stimuli.
In FL cells, interferon (IFN)-induced dsRNA-dependent protein kinase (PK-I) was found to be present in a form complexed with a potent inhibitor of its dsRNA-dependent activation. The inhibitor was readily dissociated from PK-I by DEAE-cellulose chromatography to yield a dsRNA-responsive PK-I. The inhibitor was also dissociated easily from PK-I by gel filtration through Sephacryl S-200. The apparent molecular mass of the inhibitor as estimated by gel filtration was more than 160 kilodaltons. Activity of the inhibitor was decreased on IFN treatment for 8.5 hr or on Sindbis virus infection with concomitant increase in the amount of dsRNA-activatable form of PK-I. This result implies that the inhibitor may be one of the regulatory factors of cellular PK-I activity. Longer IFN treatment (24 hr) led to recovery of the inhibitor activity, but it was overridden by an extensive net synthesis of the PK-I protein.
Saito
S
S
Department of Measles Virus, National Institute of Health, Tokyo, Japan.
Kawakita
M
M
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002848:Chromatography, DEAE-Cellulose; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000737:chemistry / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000187:drug effects / Q000502:physiology*; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology*; D012845:Sindbis Virus / Q000187:drug effects / Q000201:enzymology; D014036:Togaviridae Infections / Q000201:enzymology / Q000382:microbiology; D019892:eIF-2 Kinase
D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D012330:RNA, Double-Stranded; D007372:Interferons; D011494:Protein Kinases; D019892:eIF-2 Kinase