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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >SIGNALING THROUGH THE INTERLEUKIN 2 RECEPTOR BETA CHAIN ACTIVATES A STAT-5-LIKE DNA-BINDING ACTIVITY
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SIGNALING THROUGH THE INTERLEUKIN 2 RECEPTOR BETA CHAIN ACTIVATES A STAT-5-LIKE DNA-BINDING ACTIVITY

机译：通过白介素2受体β链信号激活STAT-5样DNA结合活性

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摘要

To explore the possible involvement of STAT factors (''signal transducers and activators of transcription'') in the interleukin 2 receptor (IL-2R) signaling cascade, murine HT-2 cells expressing chimeric receptors composed of the extracellular domain of the erythropoietin receptor fused to the cytoplasmic domains of the IL-2R beta or -gamma(c) chains were prepared. Erythropoietin or IL-2 activation of these cells resulted in rapid nuclear expression of a DNA-binding activity that reacted with select STAT response elements. Based on reactivity with specific anti-STAT antibodies, this DNA-binding activity was identified as a murine homologue of STAT-5. Induction of nuclear expression of this STAT-5-like factor was blocked by the addition of herbimycin A, a tyrosine kinase inhibitor, but not by rapamycin, an immunophilin-binding antagonist of IL-2-induced proliferation. The IL-2R beta chain appeared critical for IL-2-induced activation of STAT-S, since a mutant beta chain lacking all cytoplasmic tyrosine residues was incapable of inducing this DNA binding. In contrast, a gamma(c) mutant lacking all of its cytoplasmic tyrosine residues proved fully competent for the induction of STAT-5, Physical binding of STAT-5 to functionally important tyrosine residues within IL-2R beta was supported by the finding that phosphorylated, but not nonphosphorylated, peptides corresponding to sequences spanning Y392 and Y510 of the IL-2R beta tail specifically inhibited STAT-5 DNA binding. [References: 43]
机译：为了探讨STAT因子（“信号转导和转录激活因子”）在白介素2受体（IL-2R）信号级联反应中的可能参与，鼠HT-2细胞表达由促红细胞生成素受体胞外域组成的嵌合受体制备与IL-2Rβ或-γ（c）链的胞质结构域融合的蛋白。这些细胞的促红细胞生成素或IL-2激活导致DNA结合活性的快速核表达，该活性与选定的STAT反应元件发生反应。基于与特异性抗STAT抗体的反应性，这种DNA结合活性被鉴定为STAT-5的鼠同源物。通过添加酪氨酸激酶抑制剂除草霉素A，可阻止此STAT-5样因子的核表达诱导，但不被雷帕霉素（IL-2诱导的免疫亲和性结合拮抗剂）雷帕霉素阻断。 IL-2Rβ链似乎对IL-2诱导的STAT-S激活至关重要，因为缺少所有细胞质酪氨酸残基的突变β链不能诱导这种DNA结合。相反，缺乏所有胞质酪氨酸残基的γ（c）突变体被证明完全具有诱导STAT-5的能力。STAT-5与IL-2R beta中功能上重要的酪氨酸残基的物理结合得到了磷酸化的发现的支持。 ，但不是非磷酸化的肽，对应于跨越IL-2Rβ尾巴的Y392和Y510的序列的肽特异性抑制STAT-5 DNA结合。 [参考：43]

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