A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-alpha A in Daudi cells.
Treatment of Daudi B lymphoblastoid cells with interferon (IFN)-alpha or -beta has been reported (Yap, W. H., Teo, T. S., and Tan, Y. H. (1986) Science 234, 355-358) to cause a transient increase in the level of diacylglycerol, which is the endogenous activator of protein kinase C (PK-C). To assess the role for PK-C in the induction of 2-5A synthetase mRNA and activity by IFN-alpha in Daudi cells, we have examined the effects of PK-C inhibitors and activators. We have found that the PK-C inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), strongly inhibits the induction of 2-5A synthetase mRNA and activity by recombinant IFN-alpha A (rIFN-alpha A) and that this inhibition appears to be at a post-transcriptional level. The inhibition by H7 could not be attributed to a generalized decrease in macromolecular synthesis or to inhibition of the binding or internalization of rIFN-alpha A. Moreover, pretreatment of Daudi cells for 24 h with phorbol esters to down-regulate or desensitize PK-C substantially inhibited the subsequent induction of 2-5A synthetase mRNA and activity by rIFN-alpha A. These data suggest that PK-C activity is required for the induction of 2-5A synthetase by rIFN-alpha A. However, phorbol esters, which are potent PK-C activators, did not induce 2-5A synthetase. Taken together, our data indicate that a functional PK-C is required for 2-5A synthetase induction by rIFN-alpha A at a post-transcriptional level in Daudi cells but that activation of PK-C is not sufficient for induction of this enzyme.
Faltynek
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CR
Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick, Maryland 21701.
Princler
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Gusella
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Varesio
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Radzioch
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D013449:Sulfonamides; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*
D007370:Interferon Type I; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013449:Sulfonamides; D012313:RNA; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D015088:2',5'-Oligoadenylate Synthetase