Rosenthal L A, Winestock K D, Finbloom D S
Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892-4555, USA.
Cell Immunol. 1997 Nov 1;181(2):172-81. doi: 10.1006/cimm.1997.1208.
Despite differences in T cell responses induced by interleukin (IL)-2 and IL-7, both cytokines modulate T cell functions by activation of signal transducers and activators of transcription (STAT) proteins. We examined the contribution of the two isoforms of STAT5, STAT5A and STAT5B, to IL-2- and IL-7-induced activation of human peripheral blood T lymphoblasts. Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence (GAS), and these complexes rapidly translocated (within 1 min) into the nucleus of IL-2- or IL-7-treated cells. The kinetics of this translocation were delayed in IL-7-treated as compared to IL-2-treated cells. IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element. Both IL-2 and IL-7 induced substantial amounts of STAT5A/STAT5B heterodimerization. Moreover, we observed constitutive association of STAT3 with each STAT5 isomer. These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes.
尽管白细胞介素（IL）-2和IL-7诱导的T细胞反应存在差异，但这两种细胞因子均通过激活信号转导子和转录激活子（STAT）蛋白来调节T细胞功能。我们研究了STAT5的两种异构体STAT5A和STAT5B对IL-2和IL-7诱导的人外周血T淋巴母细胞激活的作用。这两种细胞因子均诱导了含有能够结合干扰素-γ激活序列（GAS）的复合物的STAT5A和STAT5B的组装，并且这些复合物迅速（在1分钟内）转位到经IL-2或IL-7处理的细胞的细胞核中。与经IL-2处理的细胞相比，经IL-7处理的细胞中这种转位的动力学延迟。IL-2和IL-7在诱导STAT5A和STAT5B的酪氨酸磷酸化以及促进这些STAT与固定化的GAS元件结合的能力方面相当。IL-2和IL-7均诱导了大量的STAT5A/STAT5B异二聚体形成。此外，我们观察到STAT3与每种STAT5异构体的组成性结合。这些数据表明，IL-2和IL-7以相似的方式诱导STAT异二聚体的组装，并且随后的细胞反应可能由相似的基因集的诱导所驱动。
