Les protéines de la famille CIS-SOCS : des modulateurs des effets biologiques des cytokines.

Abstract

L' intensite et la duree du signal d' activation determinent la nature de la reponse cellulaire a des cytokines. Une nouvelle famille de regulateurs negatifs de ce signal a ete recemment identifiee. Ces proteines, dont l' expression est induite par des cytokines, ont ete appelees CIS (cytokine inducible SH2-containing protein) et/ou SOCS (suppressor of cytokine signalling). L' interet grandissant porte a cette famille de proteines vient des proprietes demontrees pour trois d' entre elles: CIS, SOCS-1 et SOCS-3 inhibent la reponse aux cytokines. Ces proteines sont en effet impliquees dans le retrocontrole negatif de la voie Jak/STAT et reglent la duree du signal d' activation. Elles peuvent aussi inhiber la reponse a des cytokines differentes de celles utilisees pour induire leur expression (phenomene de cross-interference). Les proteines CIS/SOCS apparaissent donc comme des modulateurs potentiels des reponses immunitaires et inflammatoires, de l' hematopoiese et de la reponse hormonale.

This review describes the main properties of a family of cytokine-inducible proteins. CIS (cytokine inducible SH2-containing protein) and SOCS proteins (suppressor of cytokine signalling) have two conserved regions: a SH2 domain and a new motif termed the SOCS Box, located at the C-terminus of the protein. Eight members of this family have been described: CIS and SOCS-1 to -7. Three of them: CIS, SOCS-1 and SOCS-2 have been shown to inhibit cytokine signalling. These proteins appear to interfere with the Jak/STAT transduction pathway and to negatively regulate the duration of signal activation. They also have the property to inhibit the response to a cytokine different from the one used to induce their expression (cross interference). Therefore, the CIS/SOCS family of proteins are potentially important regulators of inflammatory and immune responses, modulators of hematopoiesis and hormone response.