Molecular Cloning of APRF, a Novel IFN-stimulated Gene Factor 3 p91-related Transcription Factor Involved in the gp130-mediated Signaling Pathway

Cell. 1994 Apr 8;77(1):63-71. doi: 10.1016/0092-8674(94)90235-6.

Abstract

Acute-phase response factor (APRF) is a transcription factor that binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. We report here the purification and cloning of APRF. APRF exhibits a 52.5% overall homology at the amino acid level with p91, a component of the interferon (IFN)-stimulated gene factor 3 complexes. The cloned APRF protein is tyrosine phosphorylated and translocated into the nucleus in response to IL-6, but not in response to IFN-gamma. Tyrosine phosphorylation was also observed in response to other cytokines, such as leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor, whose receptors share the IL-6 receptor signal transducer gp130. In contrast, we observed that p91 is not tyrosine phosphorylated in response to IL-6. These results suggest that this novel p91-related protein may play a major role in the gp130-mediated signaling pathway and that selective activation of p91-related factors may explain the diversity of cellular responses to different cytokines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Ciliary Neurotrophic Factor
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / genetics*
  • Growth Inhibitors / pharmacology
  • Humans
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interleukin-6 / physiology
  • Leukemia Inhibitory Factor
  • Lymphokines / pharmacology
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / pharmacology
  • Oligodeoxyribonucleotides / chemistry
  • Oncostatin M
  • Peptides / pharmacology
  • Phosphotyrosine
  • STAT3 Transcription Factor
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tissue Distribution
  • Trans-Activators*
  • Transcription Factors / genetics*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Ciliary Neurotrophic Factor
  • DNA, Complementary
  • DNA-Binding Proteins
  • Growth Inhibitors
  • IRF9 protein, human
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interleukin-6
  • Isgf3g protein, mouse
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Lymphokines
  • Nerve Tissue Proteins
  • OSM protein, human
  • Oligodeoxyribonucleotides
  • Osm protein, mouse
  • Peptides
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Oncostatin M
  • Phosphotyrosine
  • Tyrosine

Associated data

  • GENBANK/L29277
  • GENBANK/L29278