Nakajima K, Wall R
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024.
Mol Cell Biol. 1991 Mar;11(3):1409-18. doi: 10.1128/mcb.11.3.1409-1418.1991.
The events in interleukin-6 (IL-6) signal transduction leading to primary response gene activation were analyzed in murine B-cell hybridoma and plasmacytoma cells which require IL-6 for growth. IL-6 stimulation of IL-6-deprived cells resulted in the rapid and transient tyrosine phosphorylation of a 160-kDa cellular protein (p160). This was followed by the highly selective induction of two primary response genes, junB/AP-1 transcription factor and TIS11. junB and TIS11 inductions were unaffected by cycloheximide, suggesting that posttranslational modifications accounted for their activation. Activation of junB and TIS11 transcription required rapid tyrosine kinase activity as well as a different protein kinase activity sensitive to the potent kinase inhibitor, H7, and activated following p160 tyrosine phosphorylation. This H7-sensitive kinase appears to be distinct from any well-characterized protein kinase-second messenger system. On the basis of these findings, we propose that IL-6-induced signal transduction proceeds through a novel protein kinase cascade which activates junB and TIS11 gene transcription.
在依赖白细胞介素-6（IL-6）生长的小鼠B细胞杂交瘤和浆细胞瘤细胞中，分析了导致初级反应基因激活的IL-6信号转导事件。用IL-6刺激缺乏IL-6的细胞，会导致一种160kDa细胞蛋白（p160）迅速且短暂的酪氨酸磷酸化。随后，两个初级反应基因junB/AP-1转录因子和TIS11被高度选择性诱导。junB和TIS11的诱导不受放线菌酮影响，这表明翻译后修饰导致了它们的激活。junB和TIS11转录的激活需要快速的酪氨酸激酶活性以及对强效激酶抑制剂H7敏感且在p160酪氨酸磷酸化后被激活的另一种蛋白激酶活性。这种对H7敏感的激酶似乎不同于任何已明确的蛋白激酶 - 第二信使系统。基于这些发现，我们提出IL-6诱导的信号转导通过一种新型蛋白激酶级联反应进行，该级联反应激活junB和TIS11基因转录。
