Stolzenberger S, Haake M, Duschl A
Biocenter, Physiological Chemistry II, Würzburg, Germany.
Eur J Biochem. 2001 Sep;268(17):4809-14. doi: 10.1046/j.1432-1327.2001.02417.x.
The transcription factor Stat6 (signal transducer and activator of transcription 6) is activated following stimulation with interleukin (IL)-4 or IL-13. Stat6 binds via a single SH2 domain first to tyrosine-phosphorylated motifs in the IL-4Ralpha chain, and then to another Stat6 molecule, which results in the formation of active dimers. We show here that a peptide derived from the Stat6-binding region of IL-4Ralpha (Stat6BP) is an effective inhibitor when it is delivered into cells by coupling with a membrane-permeable peptide. Stat6BP completely inhibited IL-4 dependent phosphorylation of Stat6, as well as basal and IL-4 stimulated transcription from a reporter gene construct with a Stat6-dependent promoter, while IL-3 and IL-4 dependent phosphorylation of Stat5 was not affected. The inhibitory effect of Stat6BP was transient, but could be prolonged by treating the cells with the phosphatase inhibitor pervanadate.
转录因子Stat6（信号转导及转录激活因子6）在白细胞介素（IL）-4或IL-13刺激后被激活。Stat6首先通过单个SH2结构域与IL-4Rα链中的酪氨酸磷酸化基序结合，然后与另一个Stat6分子结合，从而形成活性二聚体。我们在此表明，源自IL-4Rα的Stat6结合区域（Stat6BP）的肽在与膜通透性肽偶联后导入细胞时是一种有效的抑制剂。Stat6BP完全抑制了Stat6的IL-4依赖性磷酸化，以及来自具有Stat6依赖性启动子的报告基因构建体的基础转录和IL-4刺激的转录，而Stat5的IL-3和IL-4依赖性磷酸化不受影响。Stat6BP的抑制作用是短暂的，但通过用磷酸酶抑制剂过氧钒酸盐处理细胞可以延长其作用时间。
