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

Proc Natl Acad Sci U S A. 1989 Apr;86(7):2243-7. doi: 10.1073/pnas.86.7.2243.


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+].

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / biosynthesis
  • 2',5'-Oligoadenylate Synthetase / genetics*
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Blotting, Northern
  • Bucladesine / pharmacology
  • Cells, Cultured
  • Clone Cells
  • Colforsin / pharmacology
  • Enzyme Induction
  • Gene Expression Regulation*
  • Genes*
  • Interferon Type I / physiology*
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Signal Transduction*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic / drug effects


  • Interferon Type I
  • RNA, Messenger
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Bucladesine
  • 2',5'-Oligoadenylate Synthetase
  • Tetradecanoylphorbol Acetate