Sliva D, Zhu Y X, Tsai S, Kamine J, Yang Y C
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, and Indiana Cancer Research Institute, 1044 W. Walnut Street, R4-272, Indianapolis, Indiana 46202, USA.
Biochem Biophys Res Commun. 1999 Sep 16;263(1):149-55. doi: 10.1006/bbrc.1999.1083.
Interleukin-9 (IL-9) exerts its pleiotropic effects through the IL-9 receptor (IL-9R) complex that consists of the ligand specific IL-9R alpha-chain, and the IL-2R gamma-chain. In this study, we used a modified yeast two-hybrid system to isolate cDNAs encoding proteins that interact with the intracellular domain of the human IL-9R alpha-chain (hIL-9Ralpha). We have identified Tip60, an HIV-1 Tat transcription cofactor, as an hIL-9Ralpha interacting protein. The interaction between hIL-9Ralpha and Tip60 was confirmed by coimmunoprecipitation and colocalization studies. This is the first demonstration that Tip60 associates with a membrane receptor. We also mapped amino acids 411-423 in hIL-9Ralpha and amino acids 100-147 in Tip60 to be important for interaction. Interestingly, the region in hIL-9alpha that binds Tip60 is adjacent to the site previously shown to interact with Stat3. Tip60 binds HIV-Tat and mediates Tat-dependent transactivation possibly through its histone acetyltransferase activity. Our results therefore suggest that Tip60 may act as a cofactor of Stat3 or as an adaptor protein for molecules that are important for IL-9 signaling.
白细胞介素-9（IL-9）通过由配体特异性IL-9Rα链和IL-2Rγ链组成的IL-9受体（IL-9R）复合物发挥其多效性作用。在本研究中，我们使用改良的酵母双杂交系统分离编码与人IL-9Rα链（hIL-9Rα）细胞内结构域相互作用的蛋白质的cDNA。我们鉴定出Tip60，一种HIV-1 Tat转录辅因子，作为hIL-9Rα相互作用蛋白。hIL-9Rα与Tip60之间的相互作用通过免疫共沉淀和共定位研究得到证实。这是首次证明Tip60与膜受体相关联。我们还确定hIL-9Rα中的氨基酸411 - 423和Tip60中的氨基酸100 - 147对相互作用很重要。有趣的是，hIL-9α中与Tip60结合的区域与先前显示与Stat3相互作用的位点相邻。Tip60结合HIV-Tat并可能通过其组蛋白乙酰转移酶活性介导Tat依赖性反式激活。因此，我们的结果表明Tip60可能作为Stat3的辅因子或作为对IL-9信号传导重要的分子的衔接蛋白。
