Noncanonical IFN Signaling: Mechanistic Linkage of Genetic and Epigenetic Events

Figure 1

Canonical model of IFNγ (a) and IFNα (b) signaling. (a) IFNγ cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain, causing the movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1α. The dimeric STAT1α dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation. (b) IFNα binding to its receptor subunit initiates a set of events that leads to activation of STAT1α and STAT2 and formation of a complex of STATs and p48 (ISGF3) that is translocated to the specific promoter site. This model does not account for the epigenetic events nor does it explain the specificity of cytokine signaling. NPC, nuclear pore complex.

(a)

(b)