Fig. 5. Positive and negative regulation of IFN signaling.
This model describes auto- and cross-regulatory mechanisms that modulate intracellular signaling by type I and type II IFNs. (1) Positive feedback regulation of IFN-γ signaling by increased expression of STAT1. (2) Negative feedback inhibition of IFN-γ signaling by induction of SOCS. (3) IFN-γ-mediated increase in STAT1 levels enhances STAT1 activation by IFN-α. (4) IFN-γ priming couples Syk kinase to IFN-α signaling, resulting in enhanced STAT1 activation by IFN-α. (5) Constitutive subthreshold IFN-α signaling and the association of IFNGR2 and IFNAR1 facilitate activation of STAT1 by IFNGR.