JAKS AND STATS - BIOLOGICAL IMPLICATIONS

Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hemato poietic system. These factors stimulate proliferation, differentiation , and survival signals, as well as specialized functions in host resis tance to pathogens. Although cytokines are known to activate multiple signaling pathways that together mediate these important functions, on e of these pathways, the Jak-STAT pathway, is the focus of this chapte r. This pathway is triggered by both cytokines and interferons, and it very rapidly allows the transduction of an extracellular signal into the nucleus. The pathway uses a novel mechanism in which cytosolic lat ent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT protein dimerization and nuclea r translocation. STATs then can modulate the expression of target gene s. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lac king some of these signaling molecules.