A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-αA in Daudi cells

C. R. Faltynek, G. L. Princler, G. L. Gusella, L. Varesio, D. Radzioch

Research output: Contribution to journalArticle

Abstract

Treatment of Daudi B lymphoblastoid cells with interferon (IFN)-α or -β 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-α 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-αA (rIFN-αA) 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-αA. 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-αA. These data suggest that PK-C activity is required for the induction of 2-5A synthetase by rIFN-αA. 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-αA at a post-transcriptional level in Daudi cells but that activation of PK-C is not sufficient for induction of this enzyme.

Original languageEnglish
Pages (from-to)14305-14311
Number of pages7
JournalJournal of Biological Chemistry
Volume264
Issue number24
Publication statusPublished - 1989

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2',5'-Oligoadenylate Synthetase
Protein Kinase C
Interferons
Protein C Inhibitor
Phorbol Esters
Protein Kinase Inhibitors
Messenger RNA
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Enzyme Induction
Diglycerides
Down-Regulation
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

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A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-αA in Daudi cells. / Faltynek, C. R.; Princler, G. L.; Gusella, G. L.; Varesio, L.; Radzioch, D.

In: Journal of Biological Chemistry, Vol. 264, No. 24, 1989, p. 14305-14311.

Research output: Contribution to journalArticle

Faltynek, C. R. ; Princler, G. L. ; Gusella, G. L. ; Varesio, L. ; Radzioch, D. / A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-αA in Daudi cells. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 24. pp. 14305-14311.
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T1 - A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-αA in Daudi cells

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AU - Radzioch, D.

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N2 - Treatment of Daudi B lymphoblastoid cells with interferon (IFN)-α or -β 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-α 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-αA (rIFN-αA) 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-αA. 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-αA. These data suggest that PK-C activity is required for the induction of 2-5A synthetase by rIFN-αA. 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-αA at a post-transcriptional level in Daudi cells but that activation of PK-C is not sufficient for induction of this enzyme.

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