Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα.
Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα.
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DOI：
10.1007/s00251-013-0747-0
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发表时间：
2014-02
期刊：
影响因子：
3.2
通讯作者：
Hashimoto, Keiichiro
中科院分区：
文献类型：
--
作者：
Dijkstra, Johannes M.;Takizawa, Fumio;Fischer, Uwe;Friedrich, Maik;Soto-Lampe, Veronica;Lefevre, Christophe;Lenk, Matthias;Karger, Axel;Matsui, Taei;Hashimoto, Keiichiro
白细胞介素2和15 （IL-2和IL-15）是高度分化但相关的细胞因子，具有重叠但又不同的功能，并且在医疗药物使用中具有确定的益处。目前的研究发现了爬行动物和哺乳动物中IL-2/15家族的第三个古老成员il -15样（IL-15L）的基因，迄今为止只在鱼类中报道过。IL-15L基因具有完整的开放阅读框（orf）和转录证据，以及最近的净化选择，在牛、马、羊、猪和兔中被发现。在人和小鼠中，IL-15L ORF失能。虽然推断出的IL-15L蛋白与IL-15的氨基酸一致性仅为21%，但它们具有许多与IL-15Rα受体链结合重要的IL-15残基，并且重组牛IL-15L被证明确实与IL-15Rα相互作用。最近的一项研究表明，在鱼类中，IL-2和IL-15都可以结合IL-15Rα，序列基序的比较表明，结合IL-15Rα的能力是IL-2/15/ 15l家族的祖先特征。有证据表明，导致哺乳动物的物种谱系始于三种相似的细胞因子IL-2， IL-15和IL-15L，并且在后来的进化中(1)IL-2和IL-2Rα受体链获得了新的特异性结合模式；(2)IL-15L在一些但不是所有类群的哺乳动物中丢失。本研究为了解这一强大的细胞因子家族迈出了重要的一步，并可能有助于改进其在兽医和人类医学中的应用策略。本文的在线版本（doi:10.1007/s00251-013-0747-0）包含补充材料，仅供授权用户使用。
Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine. The online version of this article (doi:10.1007/s00251-013-0747-0) contains supplementary material, which is available to authorized users.
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影响因子：
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