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Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the SOCS3 gene.[1][2] This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.


The expression of SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma.

For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3.

Overexpression of SOCS3 inhibits insulin signaling in adipose tissue and the liver, but not in muscle.[3] But deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related insulin resistance.[3]

SOCS3 contributes to both leptin resistance and insulin resistance as a result of increased ceramide synthesis.[4] For that reason, studies have shown that removal of the SOCS gene prevents against insulin resistance in obesity[3]

Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development.[5]

The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase.


SOCS3 has been shown to interact with:


There is some evidence that the expression of SOCS3 is regulated by the microRNA miR-203.[12][13]

See also


  1. Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (September 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochem Biophys Res Commun. 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833.
  2. 2.0 2.1 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 (November 1997). "Cloning and characterization of novel CIS family genes". Biochem Biophys Res Commun. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.
  3. 3.0 3.1 3.2 Jorgensen SB, O'Neill HM, Sylow L, Honeyman J, Hewitt KA, Palanivel R, Fullerton MD, Öberg L, Balendran A, Galic S, van der Poel C, Trounce IA, Lynch GS, Schertzer JD, Steinberg GR (2013). "Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity". Diabetes. 62 (1): 56–64. doi:10.2337/db12-0443. PMC 3526029. PMID 22961088.
  4. Yang G, Badeanlou L, Bielawski J, Roberts AJ, Hannun YA, Samad F (2009). "Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome". American Journal of Physiology. 297 (1): E211–E224. doi:10.1152/ajpendo.91014.2008. PMC 2711669. PMID 19435851.
  5. "Entrez Gene: SOCS3 suppressor of cytokine signaling 3".
  6. 6.0 6.1 Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (September 2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725.
  7. Hörtner M, Nielsch U, Mayr LM, Heinrich PC, Haan S (May 2002). "A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor". Eur. J. Biochem. 269 (10): 2516–26. doi:10.1046/j.1432-1033.2002.02916.x. PMID 12027890.
  8. 8.0 8.1 Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. doi:10.1074/jbc.M210552200. PMID 12403768.
  9. Dey BR, Furlanetto RW, Nissley P (November 2000). "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. 278 (1): 38–43. doi:10.1006/bbrc.2000.3762. PMID 11071852.
  10. Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (June 1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells. 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843.
  11. Cacalano NA, Sanden D, Johnston JA (May 2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. 3 (5): 460–5. doi:10.1038/35074525. PMID 11331873.
  12. Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G, Candi E (2008). "miR-203 represses 'stemness' by repressing DeltaNp63". Cell Death Differ. 15 (7): 1187–95. doi:10.1038/cdd.2008.69. PMID 18483491.
  13. Wei T, Orfanidis K, Xu N, Janson P, Ståhle M, Pivarcsi A, Sonkoly E (2010). "The expression of microRNA-203 during human skin morphogenesis". Exp Dermatol. 19 (9): 854–6. doi:10.1111/j.1600-0625.2010.01118.x. PMID 20698882.

Further reading