Suppressor of cytokine signalling explained

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.[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]

Notes and 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. 10.3109/08977194.2012.687375. 0897-7194. 3757090. 22574771.
  2. A novel cytokine‐inducible gene CIS encodes an SH2‐containing protein that binds to tyrosine‐phosphorylated interleukin 3 and erythropoietin receptors.. The EMBO Journal. 1995. 10.1002/j.1460-2075.1995.tb07281.x. Yoshimura. A.. Ohkubo. T.. Kiguchi. T.. Jenkins. N.A.. Gilbert. D.J.. Copeland. N.G.. Hara. T.. Miyajima. A.. 14. 12. 2816–2826. 7796808. 398400. 22563011. free.
  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. 10.1155/2014/630797. 24757565. en. 3976820. free.
  4. Ye. Cheng. Driver. John P.. 2016. Suppressors of Cytokine Signaling in Sickness and in Health of Pancreatic β-Cells. Frontiers in Immunology. English. 7. 169. 10.3389/fimmu.2016.00169. 27242781. 4860527. 15424776. 1664-3224. free.