Anderson D M, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, Giri J, Copeland N G, Gilbert D J, Jenkins N A
Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA.
J Biol Chem. 1995 Dec 15;270(50):29862-9. doi: 10.1074/jbc.270.50.29862.
Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding. Recently, a murine IL-15-specific alpha subunit was identified, cloned, and shown to be structurally related to IL-2R alpha. However, the murine IL-15R alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2R alpha and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15R alpha variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling, suggesting that the primary role of the alpha chains is to confer high affinity binding. At high concentrations, IL-15, like IL-2, is able to signal through a complex of IL-2R beta and -gamma in the absence of the alpha subunit. Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes. However, the distribution of expression of the IL-15R alpha is much wider than that of the IL-2R alpha, suggesting a broader range of cellular targets for IL-15.
白细胞介素 -2 和 -15（IL -2 和 IL -15）是具有重叠但不同生物学效应的细胞因子。它们的受体共享两个亚基（IL -2Rβ和 -γ链），这两个亚基对于信号转导至关重要。IL -2 受体需要一个额外的 IL -2 特异性α亚基才能实现高亲和力的 IL -2 结合。最近，一种小鼠 IL -15 特异性α亚基被鉴定、克隆，并显示在结构上与 IL -2Rα相关。然而，单独的小鼠 IL -15Rα与 IL -15 结合的亲和力比 IL -2Rα和 IL -2 结合时高 1000 倍。我们现在将这些研究扩展到人类系统，分离出三种差异剪接的人类 IL -15Rα变体，它们都能够高亲和力结合 IL -15。与 IL -2Rα一样，IL -15Rα的胞质结构域对于促有丝分裂信号传导是可有可无的，这表明α链的主要作用是赋予高亲和力结合。在高浓度下，IL -15 与 IL -2 一样，能够在没有α亚基的情况下通过 IL -2Rβ和 -γ复合物发出信号。此外，IL15RA 和 IL2RA 基因具有相似的内含子 - 外显子组织，并且在人类和小鼠基因组中紧密相连。然而，IL -15Rα的表达分布比 IL -2Rα广泛得多，这表明 IL -15 具有更广泛的细胞靶点。
