Signal transduction pathways in the induction of 2',5'-oligoadenylate synthetase gene expression by interferon α/β

C. Yan, P. B. Sehgal, I. Tamm

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Treatment of quiescent BALB/c mouse 3T3 cells with murine interferon α/β (IFN-α/β) (1000 units/ml) leads to the appearance at 4 hr of 1.7-kilobase 2',5'-oligoadenylate (2',5'-OAS) mRNA as detected by Northern blot analysis. This mRNA accumulates for at least 18 hr. Two protein kinase C activators, 1,2-dioctanoyl glycerol and phorbol 12-myristate 13-acetate, suppress, whereas the calcium ionophore ionomycin enhances, the IFN-α/β-induced expression of 2',5'-OAS mRNA. The 8-bromo and dibutyryl analogs of cAMP and the adenylate cyclase activator forskolin did not affect the induction of 2',5'-OAS mRNA by IFN-α/β. In the absence of IFN-α/β, the above agents used either singly or in combinations, did not induce 2',5'-OAS mRNA expression nor did platelet-derived growth factor (1-2 units/ml), fibroblast growth factor (6-100 ng/ml), or bovine serum (10-20%). Bovine serum also did not affect 2',5'-OAS mRNA induction by IFN-α/β. The poly(ADP)-ribose synthetase inhibitor 3-aminobenzamide suppressed IFN-α/β-induced 2',5'-OAS gene expression. These results suggest that in quiescent BALB/c 3T3 cells (i) the 2',5'-OAS gene is not responsive to the three major signal transduction pathways activated by diacylglycerol, Ca2+, and cAMP; (ii) induction of the 2',5'-OAS gene by IFN-α/β is decreased by activation of the protein kinase C pathway but enhanced by elevation of intracellular [Ca2+].

Original languageEnglish (US)
Pages (from-to)2243-2247
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Jan 1 1989


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