Sherman M A, Secor V H, Brown M A
Department of Pathology and Program in Immunology and Molecular Pathogenesis, Emory University, Atlanta, GA 30322, USA.
J Immunol. 1999 Mar 1;162(5):2703-8.
IL-4 is a pleiotropic cytokine that signals through STAT6 to direct the transactivation of multiple gene targets. In this study, we demonstrate that mast cells express a distinct STAT6 isoform. This "mast cell STAT" is a product of the STAT6 gene, but is only 65 kDa in size and appears to lack the defined C-terminal transactivation domain. Despite the presence of the conventional 94-kDa STAT6 molecule, it is the smaller isoform that associates with a consensus STAT6 binding site in extracts from IL-4-treated mast cells. This is the first evidence that STAT6 isoforms can be preferentially activated and bind to DNA in a cell-specific manner. These results imply that an additional level of specificity in the IL-4R signaling mechanism exists and may partially explain the diverse effects that IL-4 exerts on different cell types.
白细胞介素-4是一种多效性细胞因子，它通过信号转导及转录激活因子6（STAT6）发挥作用，指导多个基因靶点的反式激活。在本研究中，我们证明肥大细胞表达一种独特的STAT6异构体。这种“肥大细胞STAT”是STAT6基因的产物，但大小仅为65 kDa，似乎缺乏明确的C端反式激活结构域。尽管存在传统的94 kDa STAT6分子，但在白细胞介素-4处理的肥大细胞提取物中，与STAT6共有结合位点结合的是较小的异构体。这是首个表明STAT6异构体可被优先激活并以细胞特异性方式结合DNA的证据。这些结果表明白细胞介素-4受体信号传导机制中存在额外的特异性水平，这可能部分解释了白细胞介素-4对不同细胞类型产生的多种效应。
