Suppressor of cytokine signaling 1

Function

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3, erythropoietin (EPO), GM-CSF, and interferon-gamma (IFN-γ). The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-γ action, which is required for normal postnatal growth and survival.

Several recent viral studies have shown that viral genes, such as Tax gene product (Tax), encoded by HTLV-1, could hijack SOCS1 to inhibit host antiviral pathways, as a strategy to evade host immunity.

Interactions

The suppressor of cytokine signaling 1 has been shown to interact with:

• Tax,
• CD117,
• Colony stimulating factor 1 receptor
• Growth hormone receptor,
• IRS2,
• Janus kinase 2, and
• TEC.

References

References

1. (June 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.
2. (August 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochemical and Biophysical Research Communications.
3. "OrthoMaM phylogenetic marker: SOCS1 coding sequence".
4. "Entrez Gene: SOCS1 suppressor of cytokine signaling 1".
5. (July 2011). "Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1". Journal of Virology.
6. (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal.
7. (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". The Journal of Biological Chemistry.
8. (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". The Journal of Biological Chemistry.
9. (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". The Journal of Biological Chemistry.
10. (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal.
11. (December 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology.
12. (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature.
13. (August 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". The Journal of Biological Chemistry.
14. (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Molecular and Cellular Biology.
15. (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications.
16. (October 1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". The Journal of Biological Chemistry.