Sorting Out the SOCS Genes and Their Role in Macrophage Activation

Abstract

The suppressors of cytokine signaling (SOCS) genes were first described in a group of articles published in 1997. Since that time, much has been learned about the functional activities mediated by the corresponding proteins encoded by the SOCS genes. The SOCS gene family contains eight members: SOCS1 through SOCS7 and a highly related gene known as CISH (cytokine-inducible SH2-containing protein). Although much is known about the ability of the SOCS proteins to autoregulate responses to individual cytokines, much less is known about the ability of the SOCS proteins to cross-regulate cytokine signaling. The studies described in a new report by Bidgood et al. in this issue of JICR demonstrate that SOCS1 expression induced by one cytokine, interferon (IFN)-γ, can cross-regulate signaling induced by another cytokine, granulocyte macrophage colony-stimulating factor (GM-CSF), in murine bone marrow-derived macrophages. The authors show that the ability of SOCS1 to inhibit cytokine signaling is dose- and time-dependent. SOCS1 must reach a critical threshold level before it can exert a marked inhibitory effect on autocrine signaling through the IFN-γ receptor or paracrine signaling through the GM-CSF receptor.