科研之友
微信
新浪微博
Facebook
分享链接
摘要
Ligand binding to the cognate cytokine receptors activates intracellular signaling by recruiting protein tyrosine kinases and other protein modification enzymes. However, the roles of protein modifications other than phosphorylation remain unclear. In this study, we examine a novel regulatory mechanism of Stat5, based on its acetylation. As for phosphorylation, IL-2 induces the acetylation of signaling molecules, including Stat5, in the murine T cell line CTLL-2. Stat5 is acetylated in the cytoplasm by CREB-binding protein (CBP). Acetylated Lys(696) and Lys(700) on Stat5 are critical indicators for limited proteolysis, which leads to the generation of a truncated form of StatS. In turn, the truncated form of Stat5 prevents transcription of the full-length form of Stat5. We also demonstrate that CBP physically associates with the IL-2 receptor beta-chain. CBP, found in the nucleus in resting CTLL-2 cells, relocates to the cytoplasm after IL-2 stimulation in an MEK/ERK pathway dependent manner. Thus, IL-2 mediated acetylation plays an important role in the modulation of cytokine signaling and T cell fate.
- 出版日期2016-12-1
