Akira S, Nishio Y, Inoue M, Wang X J, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Cell. 1994 Apr 8;77(1):63-71. doi: 10.1016/0092-8674(94)90235-6.
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.
急性期反应因子（APRF）是一种转录因子，它能与在各种急性期蛋白基因启动子中鉴定出的白细胞介素-6（IL-6）反应元件结合。我们在此报告APRF的纯化和克隆。APRF在氨基酸水平上与p91具有52.5%的总体同源性，p91是干扰素（IFN）刺激基因因子3复合物的一个组分。克隆的APRF蛋白在受到IL-6刺激时发生酪氨酸磷酸化并转位到细胞核中，但对IFN-γ无反应。在受到其他细胞因子如白血病抑制因子、制瘤素M和睫状神经营养因子刺激时也观察到酪氨酸磷酸化，这些细胞因子的受体共享IL-6受体信号转导子gp130。相反，我们观察到p91在受到IL-6刺激时不会发生酪氨酸磷酸化。这些结果表明，这种新型的p91相关蛋白可能在gp130介导的信号通路中起主要作用，并且p91相关因子的选择性激活可能解释了细胞对不同细胞因子反应的多样性。
