Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
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.
Akira
S
S
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Nishio
Y
Y
Inoue
M
M
Wang
X J
XJ
Wei
S
S
Matsusaka
T
T
Yoshida
K
K
Sudo
T
T
Naruto
M
M
Kishimoto
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020934:Ciliary Neurotrophic Factor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D015850:Interleukin-6 / Q000502:physiology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D019000:Phosphotyrosine; D050796:STAT3 Transcription Factor; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D015850:Interleukin-6; C494228:Isgf3g protein, mouse; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009419:Nerve Tissue Proteins; C508351:OSM protein, human; D009838:Oligodeoxyribonucleotides; C508352:Osm protein, mouse; D010455:Peptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D053683:Oncostatin M; D019000:Phosphotyrosine; D014443:Tyrosine