Kishimoto T, Akira S, Taga T
Division of Immunology, Osaka University, Japan.
Int J Immunopharmacol. 1992 Apr;14(3):431-8. doi: 10.1016/0192-0561(92)90173-i.
Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, exerting growth promotion, growth inhibition, or specific gene expression including cellular differentiation. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. Despite its lack of IL-6 binding property, gp130 is involved in the formation of high-affinity IL-6 binding sites. This two-chain IL-6 receptor system can be applied to some other cytokine receptors, such as IL-3R, IL-5R and GM-CSFR which share a second signal-transducing component. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is a leucine zipper-containing transcription factor and is homologous to C/EBP, a liver nuclear factor. NF-IL6 is also involved in the transcriptional regulation of various acute phase protein genes IL-6-triggered association of IL-6R and gp130 on hepatocytes, through intermediate steps including serine-phosphorylation of pre-existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes.
白细胞介素-6（IL-6）是一种多功能细胞因子，作用于多种细胞，发挥促进生长、抑制生长或调控包括细胞分化在内的特定基因表达的作用。IL-6受体系统由两种膜蛋白组成，一种是配体结合链（IL-6R），另一种是无配体结合功能的信号转导子gp130，二者均属于细胞因子受体家族。IL-6与IL-6R结合会引发IL-6R与gp130的缔合，进而由gp130转导信号。尽管gp130缺乏结合IL-6的特性，但它参与了高亲和力IL-6结合位点的形成。这种双链式IL-6受体系统也适用于其他一些细胞因子受体，如IL-3R、IL-5R和GM-CSFR，它们共享一个第二信号转导成分。一种调控IL-6基因表达的核因子（NF-IL6）是一种含亮氨酸拉链的转录因子，与肝脏核因子C/EBP同源。NF-IL6也参与多种急性期蛋白基因的转录调控。IL-6引发的IL-6R与gp130在肝细胞上的缔合，通过包括对预先存在的NF-IL6蛋白进行丝氨酸磷酸化等中间步骤，导致NF-IL6与IL-6反应元件结合并激活急性期蛋白基因。
