Acute phase response factor and additional members of the interferon- stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors

R. Raz, J. E. Durbin, D. E. Levy

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Cytokines and growth factors elicit responses in target cells through induction of gene expression. Signaling mechanisms leading to gene transcription from cell surface receptors often require tyrosine phosphorylation. A family of transcription factors comprising the interferon (IFN)-stimulated gene factor 3 (ISGF3) multimeric complex are phosphorylated and activated in response to interferon. We describe a protein 50% identical to the 91-kDa subunit of ISGF3 that constitutes the acute phase response factor (APRF). This protein was rapidly activated by interleukin-6 to bind an enhancer element common to genes activated in liver cells during the acute phase response to inflammation. Remarkably, APRF was also activated by IFNα, IFNγ, epidermal growth factor, platelet-derived growth factor, colony stimulating factor-1, and the cytokines leukemia inhibitory factor and oncostatin M. The growth factors also activated a third, distinct but related, DNA-binding protein in addition to APRF and p91. This novel factor or a closely related one, but neither APRF nor p91, was also activated in lymphoid cells by interleukin-2, erythropoietin, and interleukin-3. Activation of APRF, p91, and additional members of the ISGF3 family is thus a general feature of a wide variety of signaling pathways, integrating diverse signals through common transcriptional regulators.

Original languageEnglish (US)
Pages (from-to)24391-24395
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number39
StatePublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Acute phase response factor and additional members of the interferon- stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors'. Together they form a unique fingerprint.

Cite this