Suppressor of cytokine signalling

Family of genes

Suppressor of Cytokine Signaling 2

SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway.

Genes

• CISH
• SOCS1
• SOCS2
• SOCS3
• SOCS4
• SOCS5
• SOCS6
• SOCS7

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.^[1]

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.^[2]

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.^[3]

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.^[4]

References

1. 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.
2. 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.
3. 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.
4. 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)