SOCS2 explained

Suppressor of cytokine signaling 2 is a protein that in humans is encoded by the SOCS2 gene.^{[1] [2] [3]}

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 erythropoietin, GM-CSF, IL10 and interferon-gamma (IFN-gamma). The protein encoded by this gene is found to interact with the cytoplasmic domain of insulin-like growth factor 1 receptor (IGF1R), and thus is thought to be involved in the regulation of IGF1R mediated cell signaling.^[4] Knockout studies in mice also suggested a regulatory role of this gene in IGF-1 related growth control.^{[3] [5]}

Interactions

SOCS2 has been shown to interact with insulin-like growth factor 1 receptor and erythropoietin receptor.^[6] Additionally, it acts as a substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex.^[7] It is under investigation for use in targeted protein degradation.^[8]

Further reading

• Lopaczynski W . Differential regulation of signaling pathways for insulin and insulin-like growth factor I . Acta Biochimica Polonica . 46 . 1 . 51–60 . 1999 . 10453981 . 10.18388/abp.1999_4183 . free .
• Wang J, Campbell IL . Cytokine signaling in the brain: putting a SOCS in it? . Journal of Neuroscience Research . 67 . 4 . 423–427 . February 2002 . 11835308 . 10.1002/jnr.10145 . 33269663 . free .
• Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ . The SOCS box: a tale of destruction and degradation . Trends in Biochemical Sciences . 27 . 5 . 235–241 . May 2002 . 12076535 . 10.1016/S0968-0004(02)02085-6 .
• Pezet A, Buteau H, Kelly PA, Edery M . The last proline of Box 1 is essential for association with JAK2 and functional activation of the prolactin receptor . Molecular and Cellular Endocrinology . 129 . 2 . 199–208 . May 1997 . 9202403 . 10.1016/S0303-7207(97)00063-4 . 10606236 .
• Dey BR, Spence SL, Nissley P, Furlanetto RW . Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor . The Journal of Biological Chemistry . 273 . 37 . 24095–24101 . September 1998 . 9727029 . 10.1074/jbc.273.37.24095 . free .
• Pezet A, Favre H, Kelly PA, Edery M . Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling . The Journal of Biological Chemistry . 274 . 35 . 24497–24502 . August 1999 . 10455112 . 10.1074/jbc.274.35.24497 . free .
• Yandava CN, Pillari A, Drazen JM . Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively . Genomics . 61 . 1 . 108–111 . October 1999 . 10512686 . 10.1006/geno.1999.5937 .
• Ram PA, Waxman DJ . SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms . The Journal of Biological Chemistry . 274 . 50 . 35553–35561 . December 1999 . 10585430 . 10.1074/jbc.274.50.35553 . free .
• Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS . 6 . Gigantism in mice lacking suppressor of cytokine signalling-2 . Nature . 405 . 6790 . 1069–1073 . June 2000 . 10890450 . 10.1038/35016611 . 13750159 . 2000Natur.405.1069M .
• Shen X, Hong F, Nguyen VA, Gao B . IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3 . FEBS Letters . 480 . 2–3 . 132–136 . September 2000 . 11034314 . 10.1016/S0014-5793(00)01905-0 . 84290049 . free .
• Eyckerman S, Verhee A, der Heyden JV, Lemmens I, Ostade XV, Vandekerckhove J, Tavernier J . Design and application of a cytokine-receptor-based interaction trap . Nature Cell Biology . 3 . 12 . 1114–1119 . December 2001 . 11781573 . 10.1038/ncb1201-1114 . 10228882 .
• Schultheis B, Carapeti-Marootian M, Hochhaus A, Weisser A, Goldman JM, Melo JV . Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism . Blood . 99 . 5 . 1766–1775 . March 2002 . 11861294 . 10.1182/blood.V99.5.1766 . free .
• Blumenstein M, Bowen-Shauver JM, Keelan JA, Mitchell MD . Identification of suppressors of cytokine signaling (SOCS) proteins in human gestational tissues: differential regulation is associated with the onset of labor . The Journal of Clinical Endocrinology and Metabolism . 87 . 3 . 1094–1097 . March 2002 . 11889171 . 10.1210/jcem.87.3.8463 . free .
• Biener E, Maurice S, Sandowski Y, Cohen Y, Gusakowsky EE, Hooghe R, Yoshimura A, Livnah O, Gertler A . 6 . Recombinant human CIS2 (SOCS2) protein: subcloning, expression, purification, and characterization . Protein Expression and Purification . 25 . 2 . 305–312 . July 2002 . 12135564 . 10.1016/S1046-5928(02)00013-X .

Notes and References

1. Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A . 6 . Cloning and characterization of novel CIS family genes . Biochemical and Biophysical Research Communications . 239 . 2 . 439–446 . October 1997 . 9344848 . 10.1006/bbrc.1997.7484 .
2. Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T . 6 . Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3 . Biochemical and Biophysical Research Communications . 237 . 1 . 79–83 . August 1997 . 9266833 . 10.1006/bbrc.1997.7080 .
3. Web site: Entrez Gene: SOCS2 suppressor of cytokine signaling 2.
4. Dey BR, Spence SL, Nissley P, Furlanetto RW . Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor . The Journal of Biological Chemistry . 273 . 37 . 24095–24101 . September 1998 . 9727029 . 10.1074/jbc.273.37.24095 . free .
5. Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, Davey HW, Nicola NA, Hilton DJ, Alexander WS . 6 . Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b) . Molecular Endocrinology . 16 . 6 . 1394–1406 . June 2002 . 12040024 . 10.1210/mend.16.6.0845 . free .
6. Eyckerman S, Verhee A, der Heyden JV, Lemmens I, Ostade XV, Vandekerckhove J, Tavernier J . Design and application of a cytokine-receptor-based interaction trap . Nature Cell Biology . 3 . 12 . 1114–1119 . December 2001 . 11781573 . 10.1038/ncb1201-1114 . 10228882 .
7. Kung WW, Ramachandran S, Makukhin N, Bruno E, Ciulli A . Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase . Nature Communications . 10 . 1 . 2534 . June 2019 . 31182716 . 10.1038/s41467-019-10190-4 . 6557900 . 2019NatCo..10.2534K .
8. 6 . Ramachandran S, Makukhin N, Haubrich K, Nagala M, Forrester B, Lynch D, Casement R, Testa A, Bruno E, Gitto R, Ciulli A . 2022-10-18 . Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2 . Nature Communications . 14 . 1 . 6345 . 10.1038/s41467-023-41894-3. 37816714 . 10564737 . free .