AK-STAT Signaling: From Interferons to Cytokines

50 years ago Isaacs and Lindenmann (1) first described interferons (IFNs)2 as founding members of the cytokine family. Over the next 25 years, these and several other four-helix bundle cytokines were characterized. The subsequent 25 years witnessed an exponential growth in number of four-helix bundle cytokines and their corresponding receptors. The early availability of recombinant IFNs afforded an opportunity to investigate how cytokines induce gene expression, culminating in the identification of the JAK-STAT signaling paradigm (see Fig. 1). Subsequent studies identified 7 STATs and 4 JAKs, providing important insight into how the ~50 members of the four-helix bundle cytokine family transduce their potent biological responses. This review will briefly summarize this signaling paradigm (reviewed in Refs. 2¿5) and then focus on STAT-dependent transcription