Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways.

Published

Journal Article

Interferons (IFNs) play a key role in the defense against virus infection and the regulation of cell growth and differentiation, in part through changes in specific gene transcription in target cells. We describe several differences between the signal transduction events that result in transcriptional activation of the human gene coding for a guanylate-binding protein (GBP) by alpha interferon (IFN-alpha) and gamma interferon (IFN-gamma). Activation by IFN-alpha was rapid, transient, and cycloheximide resistant. Activation by IFN-gamma was slower, sustained, and delayed by cycloheximide. IFN-gamma led to the formation of a stable intracellular signal which led to continued GBP transcription even if the ligand was withdrawn, whereas IFN-alpha-induced GBP transcription decayed rapidly if IFN-alpha was withdrawn. Perturbations of signaling pathways involving classical second messengers (cyclic AMP, Ca2+, protein kinase C) did not induce GBP transcription. However, various kinase inhibitors blocked the transcriptional response to IFN-gamma but not IFN-alpha, suggesting that a specific and possibly novel kinase is involved in gene activation by IFN-gamma.

Full Text

Duke Authors

Cited Authors

  • Lew, DJ; Decker, T; Darnell, JE

Published Date

  • December 1989

Published In

Volume / Issue

  • 9 / 12

Start / End Page

  • 5404 - 5411

PubMed ID

  • 2555698

Pubmed Central ID

  • 2555698

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.9.12.5404

Language

  • eng

Conference Location

  • United States