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白细胞介素-2(IL-2)与其靶细胞表面的IL-2受体(IL-2R)相互作用并诱导c-myc基因表达,这一过程与IL-2刺激T淋巴细胞增殖有关,但其具体机制与过程还不明了。IL-2受体由α,β,γ3亚基组成。其中α亚基可提高受体与IL-2的亲和力,而β,γ亚基与信号转导有关。有些实验认为,与IL-2R γ胞内域结合的非受体型酪氨酸激酶JAK3可能介导了IL-2对c-myc基因表达的诱导,但缺乏直接证据。为了直接验证JAK3参与了这一过程,我们构建了一个嵌合受体基因IL-2R α/γ/△NJAK3,其胞外域来自白细胞介素-2受体α亚基(IL-2Rα),跨膜部分来自IL-2R γ,胞内域来自JAK3催化功能域(△NJAK3)。将此嵌合受体转入已经稳定表达IL-2R β的小鼠成纤维细胞L929(L929 β)中,筛选到稳定表达IL-2R β和IL-2R α/γ/△NJAK3的细胞株L929 β+α/γ/△NJAK3。IL-2作用于此转基因细胞株可以诱导c-myc基因表达。由于在这个系统中,没有IL-2R γ胞内域,从而排除了结合于IL-2R γ胞内域的其他分子的干扰,因此这个实验结果为JAK3在IL-2诱导c-myc基因表达中起重要作用提供了直接证据。
Interleukin-2 (IL-2) interacts with IL-2 receptor (IL-2R) on its target cell surface and induces c-myc gene expression, which is associated with IL-2 stimulation of T lymphocyte proliferation but The specific mechanism and process is not clear. The IL-2 receptor consists of α, β, γ3 subunits. The α subunit can improve the affinity of the receptor with IL-2, while the β and γ subunits are involved in signal transduction. Some experiments suggest that JAK3, a non-receptor tyrosine kinase that binds to the intracellular domain of IL-2Rγ, may mediate the induction of c-myc gene expression by IL-2, but there is no direct evidence. To directly verify that JAK3 is involved in this process, we constructed a chimeric receptor gene IL-2R α / γ / Δ NJAK3 whose extracellular domain is derived from the interleukin-2 receptor α subunit (IL-2Rα) The membrane fraction is from IL-2R gamma and the intracellular domain is from the JAK3 catalytic domain (delta NJAK3). The chimeric receptor was transfected into mouse fibroblast L929 (L929 beta) stably expressing IL-2R beta and L929 cell line stably expressing IL-2R beta and IL-2R alpha / gamma / delta NJAK3 β + α / γ / Δ NJAK3. IL-2 acts on this transgenic cell line can induce c-myc gene expression. Because in this system, there is no IL-2R [gamma] intracellular domain, thereby disrupting the interference of other molecules that bind to the IL-2R [gamma] intracellular domain, this experimental result is that JAK3 induces c-myc gene expression in IL- The important role provided direct evidence.