Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma signal transduction in vitro and in vivo
- Author(s)
- Brysha, M; Zhang, JG; Bertolino, P; Corbin, JE; Alexander, WS; Nicola, NA; Hilton, DJ; Starr, R;
- Details
- Publication Year 2001-06-22,Volume 276,Issue #25,Page 22086-22089
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- 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 over expression 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 IFN gamma signaling in SOCS-1(-/-) mice, it is unclear to what extent this is due to increased IFN gamma levels or to increased IFN gamma sensitivity. Here we have used SOCS-1(-/-) IFN gamma (-/-) mice, which remain healthy and produce no endogenous IFN gamma to demonstrate that in vitro and in vivo hepatocytes lacking SOCS-1 exhibit a prolonged response to IFN gamma and that this correlates with a dramatically increased sensitivity to the toxic effects of IFN gamma in vivo. Thus, SOCS-1 is required for the timely attenuation of IFN gamma signaling in vivo.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- TARGETED DISRUPTION; MICE; INHIBITOR; ACTIVATION; LIVER; GENE; CELLS; STAT1; LYMPHOCYTES; PROTEINS
- Publisher's Version
- https://doi.org/10.1074/jbc.M102737200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-06-22 12:00:00