IL-4 preferentially activates a novel STAT6 isoform in mast cells

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.