Wang Y, Fuller G M
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Gene. 1995 Sep 11;162(2):285-9. doi: 10.1016/0378-1119(95)00295-h.
Interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) share a signal-transducing molecule called gp130. Previous studies showed that CNTF regulates fibrinogen gene expression in rat hepatocytes by competitive binding to the IL-6 receptor. This report explores the post ligand-binding events in the control of fibrinogen and early response gene production stimulated by IL-6 and CNTF in primary rat hepatocytes. Metabolic labeling, using [32P]orthophosphate or anti-phosphotyrosine antibody (Ab) blot experiments revealed that both IL-6 and CNTF induced tyrosine phosphorylation of gp130, and the Jak1 and Jak2 kinases in a dose- and time-dependent manner. Additional experiments revealed that only one of the early response genes, junb, but not c-myc or c-fos, was stimulated by the addition of either IL-6 or CNTF. These data suggest that activation of Jak kinases and stimulation of junb reflect a divergence of the IL-6/CNTF signaling pathway and further suggest that junb may participate in cytokine control of acute-phase protein production in the inflammatory response.
白细胞介素-6（IL-6）和睫状神经营养因子（CNTF）共用一种名为gp130的信号转导分子。先前的研究表明，CNTF通过与IL-6受体竞争性结合来调节大鼠肝细胞中纤维蛋白原基因的表达。本报告探讨了在原代大鼠肝细胞中，IL-6和CNTF刺激纤维蛋白原及早期反应基因产生过程中配体结合后的事件。使用[32P]正磷酸盐进行的代谢标记或抗磷酸酪氨酸抗体（Ab）印迹实验表明，IL-6和CNTF均以剂量和时间依赖性方式诱导gp130、Jak1和Jak2激酶的酪氨酸磷酸化。进一步的实验表明，添加IL-6或CNTF仅刺激早期反应基因之一junb，而不刺激c-myc或c-fos。这些数据表明Jak激酶的激活和junb的刺激反映了IL-6/CNTF信号通路的分歧，并且进一步表明junb可能参与炎症反应中急性期蛋白产生的细胞因子调控。
