Lack of nuclear translocation of cytoplasmic domains of IL-2/IL-15 receptor subunits.
Lack of nuclear translocation of cytoplasmic domains of IL-2/IL-15 receptor subunits.
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IL-2/IL-15 受体亚基胞质结构域缺乏核转位。
DOI：
10.1016/j.cyto.2009.02.014
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发表时间：
2009
期刊：
影响因子：
3.8
通讯作者：
Hoshino,Akemi
中科院分区：
文献类型：
--
作者：
Fujii,Hodaka;Hoshino,Akemi
一些细胞外信号分子传感器，例如Notch和甾醇反应元件结合蛋白（SREBP），接受配体诱导的膜内蛋白水解，随后其细胞质结构域发生核易位，以调节细胞核中的基因表达程序。尚未广泛研究是否发生配体诱导的 I 型细胞因子受体膜内蛋白水解和细胞质结构域的核转位。在这里，通过使用敏感的报告系统，我们检查了白介素 2 (IL-2) 受体 (IL-2R) β 链 (IL-2Rβ) 和 IL-15 受体 (IL-15R) α 链 (IL-15Rα) 的这种可能性。流式细胞术分析表明，配体刺激不会诱导其细胞质结构域的核转位。此外，在 IL-2R 重建的 Ba/F3 衍生细胞系中，常见细胞因子受体 γ 链 (γc) 胞质结构域的过度表达不会影响任何生物反应，包括细胞存活，反驳了 γc 裂解胞质结构域作为信号转导器的潜在作用。总的来说，这些结果表明裂解的 I 型细胞因子受体亚基的潜在核功能是不合理的。
Some sensors of extracellular signaling molecules such as Notch and sterol response element binding protein (SREBP) receive ligand-induced intra-membrane proteolysis followed by nuclear translocation of their cytoplasmic domains to regulate gene expression programs in the nucleus. It has not been extensively examined whether ligand-induced intra-membrane proteolysis of type I cytokine receptors and nuclear translocation of cytoplasmic domains occur. Here, by using a sensitive reporter system, we examined this possibility for the interleukin-2 (IL-2) receptor (IL-2R) β-chain (IL-2Rβ) and the IL-15 receptor (IL-15R) α-chain (IL-15Rα). Flowcytometric analysis revealed that ligand stimulation does not induce nuclear translocation of their cytoplasmic domains. In addition, overexpression of the cytoplasmic domain of the common cytokine receptor γ-chain (γc) in an IL-2R-reconstituted Ba/F3-derived cell line did not affect any biological responses including cell survival, disproving potential roles of the cleaved cytoplasmic domain of γc as a signal transducer. Collectively, these results indicated that potential nuclear function of cleaved type I cytokine receptor subunits is not plausible.