Nielsen M, Nordahl M, Svejgaard A, Odum N
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Cytokine. 1998 Oct;10(10):735-8. doi: 10.1006/cyto.1998.0356.
Signal transducer and activator of transcription 3 (Stat3) has recently been shown to exist in two alternatively spliced isoforms, a short form, Stat3beta, and a longer form, Stat3alpha, displaying differences in transcriptional activity. It is unknown which Stat3 isoform(s) is activated in response to interleukin (IL)-2 and IL-15. Here, cytokine-induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3. As determined by tyrosine phosphorylation, nuclear translocation and binding to an hSIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3alpha. In contrast, minimal or no activation of Stat3beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells. In this way, diversity in the expression and activation of Stat3 proteins may provide additional means of regulating cytokine-induced T cell responses.
信号转导子和转录激活子3（Stat3）最近被证明以两种可变剪接异构体的形式存在，一种是短形式Stat3β，另一种是较长形式Stat3α，它们在转录活性上存在差异。目前尚不清楚哪种Stat3异构体在白细胞介素（IL）-2和IL-15的刺激下被激活。在这里，我们使用针对Stat3不同区域的抗体，检测了细胞因子诱导的Stat3在先前活化的人CD4⁺T细胞中的激活情况。通过酪氨酸磷酸化、核转位以及与hSIE寡核苷酸探针的结合来确定，IL-2和IL-15激活了迁移较慢的异构体Stat3α。相比之下，未观察到Stat3β的激活或仅有极少激活，这表明IL-2和IL-15在人CD4⁺T细胞中主要激活Stat3α。通过这种方式，Stat3蛋白表达和激活的多样性可能为调节细胞因子诱导的T细胞反应提供额外的途径。
