Negative regulators of cytokine signaling.

The interaction of a cytokine with its specific cell surface receptor triggers the activation of intracellular signaling pathways that ultimately program the cellular response. Although the specific components and actions of the pathways driving these responses, such as the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, are relatively well defined, it is becoming clear that important mechanisms exist to restrain these signaling cascades. This review discusses the key biochemical actions and biological roles of the phosphatase SHP-1, the protein inhibitors of activated STATs (PIAS) and the suppressor of cytokine signaling (SOCS) protein family in the negative regulation of cytokine signal transduction.