Journal article

SOCS3 negatively regulates IL-6 signaling in vivo

BA Croker, DL Krebs, JG Zhang, S Wormald, TA Willson, EG Stanley, L Robb, CJ Greenhalgh, I Forster, BE Clausen, NA Nicola, D Metcalf, DJ Hilton, AW Roberts, WS Alexander

Nat. Immunol. | NATURE PUBLISHING GROUP | Published : 2003

Abstract

Members of the suppressor of cytokine signaling (SOCS) family are potentially key physiological negative regulators of interleukin-6 (IL-6) signaling. To examine whether SOCS3 is involved in regulating this signaling, we have used conditional gene targeting to generate mice lacking Socs3 in the liver or in macrophages. We show that Socs3 deficiency results in prolonged activation of signal transducer and activator of transcription 1 (STAT1) and STAT3 after IL-6 stimulation but normal activation of STAT1 after stimulation with interferon-gamma (IFN-gamma). Conversely, IL-6-induced STAT activation is normal in Socs1-deficient cells, whereas STAT1 activation induced by IFN-gamma is prolonged. M..

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