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.