SOCS: physiological suppressors of cytokine signaling
Abstract
Cytokines regulate cellular behavior by interacting with receptors on the plasma membrane of target cells and activating intracellular signal transduction cascades such as the JAK-STAT pathway. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling. The SOCS family consists of eight proteins: SOCS1-SOCS7 and CIS, each of which contains a central Src-homology 2 (SH2) domain and a C-terminal SOCS box. The expression of CIS, SOCS1, SOCS2 and SOCS3 is induced in response to stimulation by a wide variety of cytokines, and overexpression of these proteins in cell lines results in inhibition of cytokine signaling. Thus, SOCS roteins appear to form part of a classical negative feedback loop. The analysis of mice lacking SOCS1 has revealed that it is critical in the negative regulation of IFNγ signaling and in the differentiation of T cells. Additionally, the analysis of mouse embryos lacking SOCS3 suggests that SOCS3 negatively regulates fetal liver erythropoiesis, probably through its ability to modulate erythropoietin (Epo) signaling. Thus, the use of gene targeting has confirmed that SOCS proteins regulate cytokine signaling in a physiological setting.
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Nascent SOCS-3 blocks the activation of STAT-3 by binding to the receptor complex via gp130 at tyrosine 759 and/or by binding and inhibiting Jak2 activity.
“In the first mechanism, nascent SOCS-3 blocks the activation of STAT-3 by binding to the receptor complex via gp130 at tyrosine 759 (34,35) and/or by binding and inhibiting Jak2 activity (36).”
From Expression of suppressors of cytokine signaling during liver regeneration (2001) · cites this paper as [36]
Cites
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SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
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SOCS3 Mediates Feedback Inhibition of the Leptin Receptor via Tyr985
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Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development
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Self-citation
- Authors
- Krebs, D. L., & Hilton, D. J.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2000-08-15
- Volume
- 113
- Issue
- 16
- Pages
- 2813-2819
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1964466523
- Cited by
- 463
- References
- 1
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 11 · 2023: 1 · 2022: 7 · 2021: 11 · 2020: 14 · 2019: 7 · 2018: 13 · 2017: 15 · 2016: 16 · 2015: 19 · 2014: 19 · 2013: 15 · 2012: 22
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA22556)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- suppressor of cytokine signaling, SOCS1, SOCS3, cytokine signaling, JAK/STAT signaling, negative feedback regulation, SH2 domain, SOCS box, interferon-gamma signaling, T cell differentiation, erythropoiesis, erythropoietin signaling, gene targeting
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Animals, Carrier Proteins, DNA-Binding Proteins, Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Cytokines, Suppressor of Cytokine Signaling Proteins
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