Lai S Y, Xu W, Gaffen S L, Liu K D, Longmore G D, Greene W C, Goldsmith M A
Gladstone Institute of Virology and Immunology, San Francisco, CA 94141, USA.
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):231-5. doi: 10.1073/pnas.93.1.231.
The specific signal transduction function of the gamma c subunit in the interleukin (IL) 2, IL-4, IL-7, IL-9, and IL-15 receptor complexes remains undefined. The present structure-function analyses demonstrated that the entire cytoplasmic tail of gamma c could be functionally replaced in the IL-2 receptor (IL-2R) signaling complex by a severely truncated erythropoietin receptor cytoplasmic domain lacking tyrosine residues. Heterodimerization of IL-2R beta with either gamma c or the truncated erythropoietin receptor chain led to an array of specific signals normally derived from the native IL-2R despite the substitution of Janus kinase JAK2 for JAK3 in the receptor complex. These findings thus suggest a model in which the gamma c subunit serves as a common and generic "trigger" chain by providing a nonspecific Janus kinase for signaling program initiation, while signal specificity is determined by the unique "driver" subunit in each of the gamma c- containing receptor complexes. Furthermore, these results may have important functional implications for the asymmetric design of many cytokine receptor complexes and the evolutionary design of receptor subfamilies that share common trigger or driver subunits.
γc亚基在白细胞介素（IL）-2、IL-4、IL-7、IL-9和IL-15受体复合物中的特定信号转导功能仍不明确。目前的结构-功能分析表明，在IL-2受体（IL-2R）信号复合物中，γc的整个细胞质尾部可被一个严重截短的、缺乏酪氨酸残基的促红细胞生成素受体细胞质结构域在功能上替代。IL-2Rβ与γc或截短的促红细胞生成素受体链的异源二聚化导致了一系列通常源自天然IL-2R的特定信号，尽管受体复合物中用Janus激酶JAK2替代了JAK3。因此，这些发现提示了一种模型，即γc亚基通过提供一种非特异性的Janus激酶来启动信号程序，从而作为一个共同且通用的“触发”链，而信号特异性则由每个含γc的受体复合物中的独特“驱动”亚基决定。此外，这些结果可能对许多细胞因子受体复合物的不对称设计以及共享共同触发或驱动亚基的受体亚家族的进化设计具有重要的功能意义。
