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Gene Review

Socs2  -  suppressor of cytokine signaling 2

Mus musculus

Synonyms: 8030460M17, AI527257, AW108012, CIS-2, CIS2, ...
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Disease relevance of Socs2

  • Socs2 induction seems B cell-specific, because no induction was observed in TCDD-responsive mouse hepatoma cells or human breast cancer cells [1].
  • In particular, mice lacking SOCS2 display gigantism accompanied by evidence of deregulated GH signalling [2].
  • In cultured hepatoma cells, estrogen increased SOCS-2 and -3 mRNA levels by 2-fold in a time- and dose-dependent manner (P < 0.05) [3].
  • Small variations in SOCS2 expression levels may significantly influence the outcome of therapeutic GH or acromegaly in intestine [4].
  • Total body weight, daily weight gain, feed consumption and gain/feed, measured daily from 21 to 42 d of age, were all significantly greater (p less than .01) in the two lines with the hg/hg genotype (Ch and Gh) compared with their respective control lines (CH and GH) [5].

High impact information on Socs2

  • These findings indicate that SOCS2 promotes neuronal differentiation by blocking growth hormone-mediated downregulation of Ngn1 [6].
  • We found that expression of SOCS2, an intracellular regulator of cytokine signaling, was restricted to mouse progenitor cells and neurons in response to leukemia inhibitory factor (LIF)-like cytokines [6].
  • SOCS2 was found to bind 2 phosphorylated tyrosines on the GH receptor, and mutational analysis of these amino acids showed that both were essential for SOCS2 function [7].
  • Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase in mature body size [7].
  • This story began several years ago with the dramatic demonstration of gigantism in the SOCS2-knockout mouse [8].

Biological context of Socs2


Anatomical context of Socs2


Associations of Socs2 with chemical compounds

  • We recently reported that estrogen stimulates SOCS-2 expression and inhibits GH signaling in kidney cells [3].
  • Interestingly, SOCS2-/- mice did not differ from their wild-type littermates in glucose or insulin tolerance tests, which is in contrast with the known diabetogenic effects of GH [15].

Physical interactions of Socs2

  • GH-induced activation of STAT5 DNA binding activity was enhanced in intestine of SOCS2 null mice compared with WT control [4].

Other interactions of Socs2

  • The Pre-SH2 domains of SOCS-2 and SOCS-3 confer the specificity of their regulatory function [10].
  • Western blot analysis confirmed that Socs2 and Cyp1a1 protein levels were also induced in CH12.LX cells [1].
  • In situ hybridisation analysis showed that SOCS-1 and SOCS-3 had a low and widespread pattern of expression, whereas SOCS-2 expression was higher and tightly regulated [16].
  • In contrast, SOCS2 is less effective, and SOCS4 is ineffective at counteracting EPO-mediated events [17].
  • We also report that growth hormone inhibited Ngn1 expression and neuronal production, and this action was blocked by SOCS2 overexpression [6].

Analytical, diagnostic and therapeutic context of Socs2

  • Suppressor of cytokine signaling-2 (SOCS-2) is a member of the suppressor of cytokine signaling family, implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal transduction pathway [18].


  1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. Boverhof, D.R., Tam, E., Harney, A.S., Crawford, R.B., Kaminski, N.E., Zacharewski, T.R. Mol. Pharmacol. (2004) [Pubmed]
  2. Suppressors of cytokine signalling and regulation of growth hormone action. Greenhalgh, C.J., Alexander, W.S. Growth Horm. IGF Res. (2004) [Pubmed]
  3. Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro. Leong, G.M., Moverare, S., Brce, J., Doyle, N., Sjögren, K., Dahlman-Wright, K., Gustafsson, J.A., Ho, K.K., Ohlsson, C., Leung, K.C. Endocrinology (2004) [Pubmed]
  4. Haplotype insufficiency for suppressor of cytokine signaling-2 enhances intestinal growth and promotes polyp formation in growth hormone-transgenic mice. Michaylira, C.Z., Ramocki, N.M., Simmons, J.G., Tanner, C.K., McNaughton, K.K., Woosley, J.T., Greenhalgh, C.J., Lund, P.K. Endocrinology (2006) [Pubmed]
  5. Efficiency of growth in mice with a major gene for rapid postweaning gain. Calvert, C.C., Famula, T.R., Bernier, J.F., Khalaf, N., Bradford, G.E. J. Anim. Sci. (1986) [Pubmed]
  6. Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. Turnley, A.M., Faux, C.H., Rietze, R.L., Coonan, J.R., Bartlett, P.F. Nat. Neurosci. (2002) [Pubmed]
  7. SOCS2 negatively regulates growth hormone action in vitro and in vivo. Greenhalgh, C.J., Rico-Bautista, E., Lorentzon, M., Thaus, A.L., Morgan, P.O., Willson, T.A., Zervoudakis, P., Metcalf, D., Street, I., Nicola, N.A., Nash, A.D., Fabri, L.J., Norstedt, G., Ohlsson, C., Flores-Morales, A., Alexander, W.S., Hilton, D.J. J. Clin. Invest. (2005) [Pubmed]
  8. Knock your SOCS off! Leroith, D., Nissley, P. J. Clin. Invest. (2005) [Pubmed]
  9. Lack of Socs2 expression causes the high-growth phenotype in mice. Horvat, S., Medrano, J.F. Genomics (2001) [Pubmed]
  10. Identification of critical residues required for suppressor of cytokine signaling-specific regulation of interleukin-4 signaling. Haque, S.J., Harbor, P.C., Williams, B.R. J. Biol. Chem. (2000) [Pubmed]
  11. Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance. Egwuagu, C.E., Yu, C.R., Zhang, M., Mahdi, R.M., Kim, S.J., Gery, I. J. Immunol. (2002) [Pubmed]
  12. STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver. Davey, H.W., McLachlan, M.J., Wilkins, R.J., Hilton, D.J., Adams, T.E. Mol. Cell. Endocrinol. (1999) [Pubmed]
  13. SOCS-3 is an insulin-induced negative regulator of insulin signaling. Emanuelli, B., Peraldi, P., Filloux, C., Sawka-Verhelle, D., Hilton, D., Van Obberghen, E. J. Biol. Chem. (2000) [Pubmed]
  14. PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro. Ling, C., Billig, H. Endocrinology (2001) [Pubmed]
  15. Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects. Rico-Bautista, E., Greenhalgh, C.J., Tollet-Egnell, P., Hilton, D.J., Alexander, W.S., Norstedt, G., Flores-Morales, A. Mol. Endocrinol. (2005) [Pubmed]
  16. Expression of "suppressor of cytokine signalling" (SOCS) genes in the developing and adult mouse nervous system. Polizzotto, M.N., Bartlett, P.F., Turnley, A.M. J. Comp. Neurol. (2000) [Pubmed]
  17. Differential roles of SOCS family members in EpoR signal transduction. Jegalian, A.G., Wu, H. J. Interferon Cytokine Res. (2002) [Pubmed]
  18. Reduced bone mineral density in SOCS-2-deficient mice. Lorentzon, M., Greenhalgh, C.J., Mohan, S., Alexander, W.S., Ohlsson, C. Pediatr. Res. (2005) [Pubmed]
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