In response to IL-12 binding, the IL-12 receptor activates the Jak kinases, which phosphorylate tyrosine residues of IL-12RB2. These phosphorylated receptors recruit Stat4 through its SH2 domain, whereupon Stat4 is phosphorylated at Tyr693 in its C-terminal transactivation domain. Phosphorylation promotes Stat4 homodimerization and translocation to the nucleus, where it promotes gene transcription. The N-terminal domain of Stat4 appears to be required for maximal stabilization and for the binding of Stat4 dimers to lower-affinity DNA binding sites. Stat4-deficient mice have demonstrated that this gene is required to both promote Th1 development and inhibit Th2 differentiation due to disabling IL-12 receptor-mediated responses.