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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Ciliary Neurotrophic Factor
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Cloning, Molecular
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics*
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Growth Inhibitors / pharmacology
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Humans
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interleukin-6 / physiology
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Leukemia Inhibitory Factor
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Lymphokines / pharmacology
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Mice
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Molecular Sequence Data
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Nerve Tissue Proteins / pharmacology
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Oligodeoxyribonucleotides / chemistry
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Oncostatin M
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Peptides / pharmacology
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Phosphotyrosine
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STAT3 Transcription Factor
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction
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Tissue Distribution
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Trans-Activators*
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Transcription Factors / genetics*
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
Substances
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Ciliary Neurotrophic Factor
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DNA, Complementary
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DNA-Binding Proteins
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Growth Inhibitors
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IRF9 protein, human
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interleukin-6
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Isgf3g protein, mouse
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LIF protein, human
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Leukemia Inhibitory Factor
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Lif protein, mouse
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Lymphokines
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Nerve Tissue Proteins
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OSM protein, human
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Oligodeoxyribonucleotides
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Osm protein, mouse
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Peptides
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Transcription Factors
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Oncostatin M
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Phosphotyrosine
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Tyrosine
Associated data
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GENBANK/L29277
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GENBANK/L29278