Biochemical approaches to discovering modulators of the JAK-STAT pathway

Regulation of cytokine activity has application in the treatment of numerous diseases, as illustrated by the successful clinical use of recombinant cytokines. The discovery of two key families of signaling - proteins the Janus kinases (JAKs) and the signal transducers and activators of transcription (STATs)-has greatly increased our understanding of cytokine signal transduction. This review describes some of the key interactions between JAKs. STATs and other components of the signal transduction cascade, and the potential for developing high-throughput biochemical screens for the detection of small molecules that target these interactions. Novel compounds of this type have potential as agonists or antagonists of cytokine action.