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Lack of nuclear translocation of cytoplasmic domains of IL-2/IL-15 receptor subunits.

机译:缺乏IL-2 / IL-15受体亚基胞质域的核易位。

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摘要

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) beta-chain (IL-2R beta) and the IL-15 receptor (IL-15R) alpha-chain (IL-15R alpha). 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 gamma-chain (gamma c) 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 gamma c as a signal transducer. Collectively, these results indicated that potential nuclear function of cleaved type I cytokine receptor subunits is not plausible.
机译:诸如Notch和固醇反应元件结合蛋白(SREBP)等胞外信号分子的某些传感器接受配体诱导的膜内蛋白水解,随后对其胞质域进行核易位,以调节细胞核中的基因表达程序。尚未广泛检查是否发生配体诱导的I型细胞因子受体的膜内蛋白水解和细胞质结构域的核易位。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)beta链(IL-2R beta)和IL-15受体(IL-15R)alpha的可能性链(IL-15R alpha)。流式细胞仪分析表明配体刺激不会诱导其胞质域的核易位。另外,在IL-2R重组的Ba / F3衍生的细胞系中,普通细胞因子受体γ链(γc)的胞质域的过表达不会影响任何生物学反应,包括细胞存活,从而证明了裂解后的潜在作用γc的胞质域作为信号转导子。总的来说,这些结果表明,被切割的I型细胞因子受体亚基的潜在核功能是不合理的。

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