The classical model of JAK-STAT signaling suggests that phosphorylated Signal transducer and activator of transcription (STAT) translocates to the nucleus (Akira et al. 1994) where it binds DNA to mediate the effects of Interleukin-13 (IL13) on expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, with important consequences for their ability to activate and sustain immune and inflammatory responses.
Recently, STATs have been shown to shuttle freely between the cytoplasm and the nucleus, independent of tyrosine phosphorylation (Liu et al. 2005, Li 2008, Reich 2013). Binding of unphosphorylated STAT3 to DNA has been reported (Nkansah et al. 2013). As it is not clear what triggers nuclear accumulation of STATs in response to IL13, this event is shown as an uncertain process.