The mechanism by which interleukin-4 (IL-4) regulates the expression o
f particular genes is unknown. We have determined that IL-4 induces a
DNA binding factor (termed STF-IL-4) which has a strong affinity for a
n IFN-gamma activation site (GAS). Interestingly, STF-IL-4 also binds
to the IL-4 responsive promoter for the Ig heavy chain germline epsilo
n transcript. The IL-4 dependent activation of STF-IL-4 is rapid, does
not require protein synthesis and results in the sequential appearanc
e of binding activity first in the cytoplasm and then later in the nuc
leus. Activation of STF-IL-4 is sensitive to tyrosine kinase inhibitor
s and the active factor is tyrosine phosphorylated. This pattern of ac
tivation is similar to the activation of interferon-induced transcript
ion factors. STF-IL-4 appears to be a new member of a growing family o
f cytokine-induced transcriptional regulators.