SOCS: suppressors of cytokine signalling

Regulation of many aspects of cell behaviour occurs through the interaction of cytokines with specific cell surface receptors, resulting in the activation of cytoplasmic signal transduction pathways. Although cellular responses to cytokines are tightly controlled, few molecules have been identified which are able to switch these signals off. The suppressors of cytokine signalling (SOCS) proteins are a new family of negative regulators of cytokine signal transduction. SOCS proteins contain a variable amino-terminal region, a central Src-homology 2 (SH2) domain and a novel conserved carboxy-terminal motif termed the SOCS box. The expression of SOCS proteins is induced by cytokine. Once expressed, SOCS downregulate JAK/STAT pathways and hence the biological response. Recent studies, primarily reliant on overexpression of proteins, indicate that SOCS may be involved in modulating additional pathways, suggesting that they may play a more general role in regulating cellular responses to cytokine. The analysis of knockout mice will clarify the physiological role of SOCS in regulating cytokine responsiveness. Mutations leading to the loss of SOCS activity may give rise to cytokine hyperresponsiveness and may contribute to the development of diseases such as diabetes and cancer. Small molecule effecters which modify SOCS function may potentially be useful therapeutics for the treatment of certain diseases. (C) 1998 Elsevier Science Ltd. All rights reserved.