Kamogawa Y, Lee H J, Johnston J A, McMahon M, O'Garra A, Arai N
Department of Cell Signaling, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
J Immunol. 1998 Aug 1;161(3):1074-7.
Binding of IL-4 to its cognate receptor leads to the activation of a number of signaling pathways within the cell. Activation of the transcription factor STAT6 by JAK family protein tyrosine kinases has been shown to be essential for the full response of cells to IL-4. To elucidate the role of STAT6 in IL-4 signaling, we have constructed and expressed in cells a conditionally active form of the protein (STAT6:ER*) by fusing STAT6 to a modified form of the hormone-binding domain of the estrogen receptor. Activation of STAT6:ER* by 4-hydroxytamoxifen leads to specific activation of STAT6-regulated gene expression including the activation of a STAT6 reporter construct and induction of CD23 in B cell lines. Interestingly, in contrast to native STAT6, activation of STAT6:ER* occurs in the absence of detectable tyrosine phosphorylation of the fusion protein. This type of conditional system will be helpful in dissecting the mechanisms and specificity of transcriptional regulation by the STAT family of transcription factors.
白细胞介素-4（IL-4）与其同源受体结合会导致细胞内多条信号通路的激活。JAK家族蛋白酪氨酸激酶对转录因子STAT6的激活已被证明对于细胞对IL-4的充分应答至关重要。为了阐明STAT6在IL-4信号传导中的作用，我们构建了一种蛋白的条件活性形式（STAT6:ER*）并在细胞中进行表达，方法是将STAT6与雌激素受体的激素结合域的修饰形式融合。4-羟基他莫昔芬对STAT6:ER的激活会导致STAT6调控的基因表达的特异性激活，包括STAT6报告基因构建体的激活以及B细胞系中CD23的诱导。有趣的是，与天然STAT6不同，STAT6:ER的激活在融合蛋白未检测到酪氨酸磷酸化的情况下发生。这种类型的条件系统将有助于剖析STAT家族转录因子的转录调控机制和特异性。
