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 language | English |
|---|---|
| Pages (from-to) | 14305-14311 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 264 |
| Issue number | 24 |
| Publication status | Published - 1989 |
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- 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 journal › Article
}
TY - JOUR
T1 - A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-αA in Daudi cells
AU - Faltynek, C. R.
AU - Princler, G. L.
AU - Gusella, G. L.
AU - Varesio, L.
AU - Radzioch, D.
PY - 1989
Y1 - 1989
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.
AB - 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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M3 - Article
C2 - 2474543
AN - SCOPUS:0024316698
VL - 264
SP - 14305
EP - 14311
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 24
ER -