The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway
transmits information received from extracellular polypeptide signals, through
transmembrane receptors, directly to target gene promoters in the nucleus, providing
a mechanism for transcriptional regulation without second messengers. Evolutionarily
conserved in eukaryotic organisms from slime molds to humans, JAK-STAT
signaling appears to be an early adaptation to facilitate intercellular communication
that has co-evolved with myriad cellular signaling events. This co-evolution has
given rise to highly adapted, ligand-specific signaling pathways that control gene
expression. In addition, the JAK-STAT signaling pathways are regulated by a vast
array of intrinsic and environmental stimuli, which can add plasticity to the response
of a cell or tissue.