Jak-STAT Signaling Pathways

The Jak-STAT pathway is an elegant, streamlined intracellular signal transduction cascade linking extracellular cytokines with nuclear gene transcription. In its typical form, Jak-STAT signaling initiates upon high affinity interaction between cytokines and cell surface transmembrane receptors. This results in activation of receptor-associated Jak protein tyrosine kinases and stimulation of a family of transcriptional regulators known as STATs. Despite a broad array of cytokines and receptors, only 4 Jak family members and 7 STAT proteins are responsible for the accurate delivery of unique cytokine cues, which result in specific cellular responses. Thus, understanding how specificity in cytokine signaling is achieved is of principal interest. To address this, we provide an introduction in the basics of Jak-STAT signal transduction, including major positive and negative regulators of the signaling cascade. We include a brief discussion of how the Jak-STAT pathway was originally discovered through sophisticated studies in a small number of labs. Last, we present a current understanding of mechanisms that contribute to Jak-STAT signaling specificity. Collectively, the Jak-STAT cascade provides an outstanding example of how fundamental research led to the rapid discovery of a major signal transduction pathway linked with important immunological processes as well as many human diseases.