IFNγ signaling—Does it mean JAK–STAT?

The molecular pathways involved in the cellular response to interferon (IFN)γ have been the focus of much research effort due to their importance in host defense against infection and disease, as well as its potential as a therapeutic agent. The discovery of the JAK–STAT signaling pathway greatly enhanced our understanding of the mechanism of IFNγ-mediated gene transcription. However, in recent years it has become apparent that other pathways, including MAP kinase, PI3-K, CaMKII and NF-κB, either co-operate with or act in parallel to JAK–STAT signaling to regulate the many facets of IFNγ biology in a gene- and cell type-specific manner. The complex interactions between JAK/STAT and alternate pathways and the impact of these signaling networks on the biological responses to IFNγ are beginning to be understood. This review summarizes and appraises current advances in our understanding of these complex interactions, their specificity and proposed biological outcomes.