Acute-phase response factor (APRF) is a transcription factor that blnds to the Interfeukln-6 (IL-@-responsive elements identlfled In the promoters of various acutephase protein genes. We report here the puriflcatlon and cloning of APRF. APRF exhibits a 52.5% overall homology at the amino acid level wlth~ 91, a component of the interferon (IFN)-stimulated gene factor 3 complexes. The cloned APRF protein Is tyroslne phosphorylated and translocated Into the nucleus In response to lL-6, but not in response to 1FN-y. Tyrosine phosphorylatlon was also observed in response to other cytoklnes, such as leukemia inhibitory factor, oncostatln M, and clllary neurotrophlc factor, whose receptors share the IL-6 receptor signal tmnsducer gp130. In contmst, we observed that p91 Is not tyrosine phosphorylated In response to IL-6. These results suggest that this novel p91-mlated protein may play a major role In the gpl30-mediated signaling pathway and that selective activation of p91-mlated factors may explain the diversity of cellular responses to different cytoklnes.