Suppressors of Cytokine Signaling (SOCS): Inhibitors of the JAK/STAT Pathway

The suppressors of cytokine signaling (SOCS) are recently identified inhibitors of cytokine and growth factor (GF) signaling that act via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Cytokine-mediated JAK/STAT signaling controls a number of important biologic responses, including immune function, cellular growth, differentiation, and hematopoieses. The SOCS family consists of eight proteins: CIS and SOCS1-SOCS7, which contain a central SH2 domain, a conserved C-terminus referred to as the SOCS box, and a unique N-terminus. The expression of SOCS-1 to -3 and CIS is induced by cytokine or GF stimulation, resulting in the inhibition of JAK/STAT-mediated cytokine signaling by what appears to be a classic negative feedback loop. In this article we review cytokine/GF signaling by the JAK/STAT pathway, discovery of the SOCS family, the regulation of SOCS expression, mechanism(s) of SOCS action, and we summarize some of the biochemical and genetic studies investigating the physiologic role of SOCS in regulating cytokine activity.