SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway.
Genes
Structure
All SOCS have certain structures in common. This includes a varying N-terminal domain involved in protein-protein interactions, a central SH2 domain, which can bind to molecules that have been phosphorylated by tyrosine kinases, and a SOCS box located at the C-terminal that enables recruitment of E3 ligases and ubiquitin signaling molecules.
Discovery
The first protein to be classified as a suppressor of cytokine signaling, CIS (cytokine-inducible SH2), was discovered in 1995, when it was found to have a unique ability to regulate cytokine signal transduction.
Function
SOCS are negative regulators of the JAK-STAT signaling pathway. SOCS have also been implicated in the regulation of cytokines, growth factors, and tumor suppression.
Role in Disease
It has been suggested that SOCS can help prevent cytokine-mediated apoptosis in diabetes through negative regulation of pro-inflammatory cytokines secreted by immune cells, such as IFNγ, TNFα and IL-15. Improper functioning of one specific SOCS, SOCS3 may lead to type 2 diabetes, as it has been found that SOCS3 plays an important role in proper leptin signaling.
References
- Babon, Jeffrey; Nicola, Nicos A (August 2012). "The biology and mechanism of action of Suppressor of Cytokine Signaling 3 (SOCS3)". Growth Factors. 30 (4): 207–219. doi:10.3109/08977194.2012.687375. ISSN 0897-7194. PMC 3757090. PMID 22574771.
- Yoshimura, A.; Ohkubo, T.; Kiguchi, T.; Jenkins, N.A.; Gilbert, D.J.; Copeland, N.G.; Hara, T.; Miyajima, A. (1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". The EMBO Journal. 14 (12): 2816–2826. doi:10.1002/j.1460-2075.1995.tb07281.x. PMC 398400. PMID 7796808. S2CID 22563011.
- Sasi, Walid; Sharma, Anup K.; Mokbel, Kefah (2014-03-16). "The Role of Suppressors of Cytokine Signalling in Human Neoplasms". Molecular Biology International. 2014: 630797. doi:10.1155/2014/630797. PMC 3976820. PMID 24757565.
- Ye, Cheng; Driver, John P. (2016). "Suppressors of Cytokine Signaling in Sickness and in Health of Pancreatic β-Cells". Frontiers in Immunology. 7: 169. doi:10.3389/fimmu.2016.00169. ISSN 1664-3224. PMC 4860527. PMID 27242781. S2CID 15424776.
External links
- Suppressor+of+Cytokine+Signaling+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
| JAK-STAT signaling pathway | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligand | |||||||||
| Cytokine receptor | |||||||||
| Janus kinase | |||||||||
| Adaptor proteins |
| ||||||||
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