Ohbo K, Takasawa N, Ishii N, Tanaka N, Nakamura M, Sugamura K
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
J Biol Chem. 1995 Mar 31;270(13):7479-86. doi: 10.1074/jbc.270.13.7479.
The third component of the interleukin (IL) 2 receptor, gamma chain, is essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and IL-15-induced proliferation of lymphocytes. To elucidate the mechanisms by which the gamma chain is expressed, we have analyzed the promoter region of the gamma chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoietic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA start site, including an Ets binding sequence. Treatment of cells with either 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but not forskolin induced transcription from the gamma chain gene promoter. A viral trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I elevated expression of the gamma chain gene. In contrast, IL-2 decreased transcription from the IL-2 receptor gamma chain promoter. These results suggest that expression of the gamma chain is regulated at the transcription level by extracellular stimuli and may be implicated in immune response.
白细胞介素(IL)-2受体的第三个组成部分——γ链,不仅对IL-2诱导的淋巴细胞增殖至关重要,对IL-4、IL-7、IL-9和IL-15诱导的淋巴细胞增殖也必不可少。为了阐明γ链表达的机制,我们分析了γ链基因的启动子区域。起始密码子上游633个碱基对的片段与荧光素酶基因相连时,在人造血细胞系Jurkat和THP-1中显示出启动子活性。通过一系列5'-缺失突变体,发现基础启动子活性存在于RNA起始位点上游核苷酸80至58的片段中,该片段包含一个Ets结合序列。用12-O-十四酰佛波醇-13-乙酸酯或植物血凝素处理细胞可诱导γ链基因启动子转录,但用福斯高林处理则不能。人T细胞白血病病毒I型的病毒反式作用转录激活因子Tax可提高γ链基因的表达。相反,IL-2可降低IL-2受体γ链启动子的转录。这些结果表明,γ链的表达在转录水平受细胞外刺激调节,可能与免疫反应有关。