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.
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 1989|
ASJC Scopus subject areas