Negative regulators of cytokine signal transduction

Enormous advances have been made over the last 10 years in unravelling cytokine signal transduction. This work has led to the recognition of the prime importance of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). More recently, the importance of negative regulators of this pathway has begun to be realised. There is now evidence for at least three families of proteins that inhibit JAK/STAT signalling. The suppressors of cytokine signalling (SOCS), protein inhibitors of activated STATs (PIAS) and the SH2-containing phosphatase (SHP-1). This review describes some of the key features of SOCS proteins and contrasts their actions with other negative regulators, the PIAS proteins and SHP-1.