Signal transduction pathways in the induction of 2',5'-oligoadenylate synthetase gene expression by interferon alpha/beta.
Treatment of quiescent BALB/c mouse 3T3 cells with murine interferon alpha/beta (IFN-alpha/beta) (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-alpha/beta-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-alpha/beta. In the absence of IFN-alpha/beta, 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-alpha/beta. The poly(ADP)-ribose synthetase inhibitor 3-aminobenzamide suppressed IFN-alpha/beta-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-alpha/beta is decreased by activation of the protein kinase C pathway but enhanced by elevation of intracellular [Ca2+].
Yan
C
C
Rockefeller University, New York, NY 10021.
Sehgal
P B
PB
Tamm
I
I
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D005796:Genes; D007370:Interferon Type I / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D007370:Interferon Type I; D012333:RNA, Messenger; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D015088:2',5'-Oligoadenylate Synthetase; D013755:Tetradecanoylphorbol Acetate