Cellular and Molecular Life Sciences CMLS

, Volume 55, Issue 12, pp 1568-1577

First online:

Negative regulators of cytokine signal transduction

  • D. J. HiltonAffiliated withThe Walter and Eliza Hall Institute of Medical Research and The Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Victoria 3050 (Australia), Fax +61 3 9345 2616, e-mail: hilton@wehi.edu.au

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Abstract.

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 supressors 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.

Key words. Cytokines; signal transduction; negative regulation.