Suppressor of Cytokine Signaling-1 Attenuates the Duration of Interferon γ Signal Transduction in Vitro and in Vivo
Open accessAbstract
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.
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STAT1 tyrosine phosphorylation in response to IFNγ was prolonged in the absence of SOCS1.
“Consistent with previous observations (30), STAT1 tyrosine phosphorylation in response to IFN␥ was prolonged in the absence of SOCS1 (Fig. 4A).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [30]
IFNγ signaling was simply attenuated in duration by SOCS1, a finding consistent with previous observations.
“In contrast to the bi-phasic manner in which IL-6 signaling was regulated by SOCS3, IFN␥ signaling was simply attenuated in duration by SOCS1, a finding consistent with previous observations (30).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [30]
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Research works printed but not linked: 6
- Hilton, D. J., Richardson, R. T., Alexander, W. S., Viney, E. M., Willson, T. A., Sprigg, N. S., Starr, R., Nicholson, S. E., Metcalf, D., and Nicola, N. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 114 -119
- Starr, R., Metcalf, D., Elefanty, A. G., Brysha, M., Willson, T. A., Nicola, N. A., Hilton, D. J., and Alexander, W. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 14395-14399
- Naka, R., Matsumoto, T., Narazaki, M., Fujimoto, M., Morita, Y., Ohsawa, Y., Saito, H., Nagasawa, T., Uchiyama, Y., and Kishimoto, T. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 15577-15582
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Jeong, W.-I., Park, O., Suh, Y.-G., Byun, J.-S., Park, S.-Y., Choi, E., Kim, J.-K., Ko, H., Wang, H., Miller, A. M., et al. (2011) · Hepatology · doi:10.1002/hep.24190 · Cited by 142 · see citing works
Wormald, S., Zhang, J.-G., Krebs, D. L., Mielke, L. A., Silver, J., Alexander, W. S., Speed, T. P., Nicola, N. A., & Hilton, D. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509595200 · Cited by 123 · see citing works
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- Authors
- Brysha, M., Zhang, J.-G., Bertolino, P., Corbin, J. E., Alexander, W. S., Nicola, N. A., Hilton, D. J., & Starr, R.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Starr, Robyn
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 276
- Issue
- 25
- Pages
- 22086-22089
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1981299945
- Cited by
- 102
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Australian Government
- National Institutes of Health (CA22556)
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- National Cancer Institute (CA22556)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- SOCS1, interferon-gamma, interferon signaling, negative regulation of cytokine signaling, hepatocytes, liver degeneration
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Animals, Carrier Proteins, Interferon-gamma, Mice, Inbred Strains, Repressor Proteins, Signal Transduction, Hepatocytes, Suppressor of Cytokine Signaling Proteins, Mice, In Vitro Techniques
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