John Libbey Eurotext

Hématologie

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SOCS proteins: regulators of cytokine signal transduction Volume 6, issue 4, Juillet - Août 2000

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Inserm U. 119, 27, boulevard Lei-Roure, 13009 Marseille.

Cytokines are involved at all stages of hematopoiesis to control the survival, the proliferation and the differentiation of hematopoietic cells. Because cytokines have such a critical function, the transduction of signals through cytokine receptors is a highly regulated process. Accumulated evidence indicates that the Socs (suppressors of cytokine signaling) proteins, (a recently described family of SH2-domain containing proteins) play a central role in the negative regulation of cytokine signalling. The transcription of the Socs genes is induced by various cytokines and the Socs proteins in turn suppress or modulate signalling pathways activated by cytokine receptors. One of the main targets of Socs-mediated inhibition is the Jak/Stat pathway. The mechanisms by which Socs proteins interfere with this pathway include direct inhibition of the catalytic activity of Jak kinases and competition between Socs and Stat proteins for the same binding sites on activated receptors. Structurally, Socs proteins are made of three domains which are all potentially involved in the recruitement of partner proteins. Recent evidence suggest that Socs proteins could act as adapter proteins linking protein substrates to the ubiquitin machinary through the interaction of Socs with ubiquitin ligase complexes. The models and mechanisms of inhibition of cytokine signalling by Socs and the physiological functions of Socs proteins are discussed in this review.