title: Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma signal transduction in vitro and in vivo.
abstract: Suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible intracellular protein that functions to negatively regulate cytokine signal transduction pathways. Studies in vitro have shown that constitutive overexpression of SOCS-1 inhibits signaling in response to a range of cytokines, including interferons (IFN). Mice lacking SOCS-1 die from a complex disease characterized by liver degeneration and massive inflammation. Whereas there is clear evidence of increased IFNgamma signaling in SOCS-1(-/-) mice, it is unclear to what extent this is due to increased IFNgamma levels or to increased IFNgamma sensitivity. Here we have used SOCS-1(-/-) IFNgamma(-/-) mice, which remain healthy and produce no endogenous IFNgamma, to demonstrate that in vitro and in vivo hepatocytes lacking SOCS-1 exhibit a prolonged response to IFNgamma and that this correlates with a dramatically increased sensitivity to the toxic effects of IFNgamma in vivo. Thus, SOCS-1 is required for the timely attenuation of IFNgamma signaling in vivo.
authors: Cooperative Research Center for Cellular Growth Factors and the Walter and Eliza Hall Institute for Medical Research, PO Royal Melbourne Hospital, Newtown New South Wales 2042, Australia.
authors: M
authors: M
authors: Brysha
authors: J G
authors: JG
authors: Zhang
authors: P
authors: P
authors: Bertolino
authors: J E
authors: JE
authors: Corbin
authors: W S
authors: WS
authors: Alexander
authors: N A
authors: NA
authors: Nicola
authors: D J
authors: DJ
authors: Hilton
authors: R
authors: R
authors: Starr
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
chemical_list: D002352:Carrier Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma