A conditionally active form of STAT6 can mimic certain effects of IL-4

Abstract

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.