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Gene Review

SOCS2  -  suppressor of cytokine signaling 2

Homo sapiens

Synonyms: CIS-2, CIS2, Cish2, Cytokine-inducible SH2 protein 2, SOCS-2, ...
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Disease relevance of SOCS2


High impact information on SOCS2

  • Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent [5].
  • Upon infection with an intracellular pathogen, SOCS-2-deficient mice had uncontrolled production of proinflammatory cytokines, decreased microbial proliferation, aberrant leukocyte infiltration and elevated mortality [5].
  • SOCS-2 overexpression in Caco-2 cells inhibited cell proliferation and promoted differentiation [6].
  • CONCLUSIONS: SOCS-2 is a GH-inducible, novel inhibitor of intestinal epithelial cell proliferation and intestinal growth [6].
  • The inhibitory effect of E(2) was absent in cells lacking SOCS-2 but not in those lacking SOCS-1 and SOCS-3 [7].

Chemical compound and disease context of SOCS2

  • The cisplatin-resistant gastric cancer cell sublines, SNU-601/Cis2 and /Cis10, were 49 and >530 times more resistant to cisplatin, respectively, compared with the drug-sensitive cells, SNU-601/WT [8].

Biological context of SOCS2


Anatomical context of SOCS2

  • Using reverse transcriptase (RT)-PCR and Western blot analysis we investigated the expression of SOCS1, SOCS2, and SOCS3 mRNA and protein, respectively, by human villous placenta, amnion and choriodecidua (n = 3-4) [9].
  • Cells transfected with eight of these tagged constructs expressed the fluorescent proteins in both the nucleus and cytosol; the tagged SOCS2 was localized mostly in the latter compartment [13].
  • The intravenous hGH did not induce SOCS2 mRNA expression in the hypothalamus [14].
  • In addition, several studies indicate that SOCS2 also has important actions in the central nervous system, the regulation of metabolism, the immune response, the mammary gland development, cancer, and other cytokine-dependent signaling pathways [10].
  • Glutathione S-transferase-hSOCS-2 associated with activated IGF-IR in lysates of mouse fibroblasts overexpressing IGF-IR [15].

Associations of SOCS2 with chemical compounds

  • This paper provides evidence for regulatory interaction between a sex steroid and the GHJAKSTAT pathway, in which SOCS-2 plays a central mechanistic role [7].
  • In conclusion, estrogen inhibits GH signaling, an action mediated by SOCS-2 [7].
  • Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with hSOCS-2 protein. hSOCS-1 protein also interacted strongly with IGF-IR in the two-hybrid assay [15].
  • Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion [16].
  • We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells [17].

Physical interactions of SOCS2

  • Here, we show that CIS (cytokine-inducible SH2 protein) and SOCS2 can also interact with the leptin receptor [18].
  • However, 55PIK and SOCS-2 also interact with the IR in the yeast two hybrid system [19].

Regulatory relationships of SOCS2

  • In a yeast two-hybrid screen of a human fetal brain library, we have previously identified SOCS-2 as a binding partner of the activated IGF-I receptor (IGFIR) [20].

Other interactions of SOCS2

  • Interferon (IFN)-gamma treatment induces the expression of SOCS1, SOCS2, and SOCS3 mRNAs [21].
  • Specific studies targeting the SOCS genes in vivo have unveiled SOCS2 as the main regulator of somatic growth through regulation of GH/IGF-1 signaling [10].
  • SOCS1, SOCS2, RASSF1a, CDKN2a, and MGMT were methylated in 75, 43, 64, 75, and 64% of melanoma samples, respectively [22].
  • Jurkat cells expressed more SOCS-2 when exposed to PRL [23].
  • RESULTS: SOCS-2 protein was expressed in 34 of 50 breast carcinoma samples and was positively associated with low grade, low nuclear grade, and p27 protein [24].

Analytical, diagnostic and therapeutic context of SOCS2


  1. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Sutherland, K.D., Lindeman, G.J., Choong, D.Y., Wittlin, S., Brentzell, L., Phillips, W., Campbell, I.G., Visvader, J.E. Oncogene (2004) [Pubmed]
  2. Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. Federici, M., Giustizieri, M.L., Scarponi, C., Girolomoni, G., Albanesi, C. J. Immunol. (2002) [Pubmed]
  3. A proinflammatory cytokine response is present in the fetal placental vasculature in placental insufficiency. Wang, X., Athayde, N., Trudinger, B. Am. J. Obstet. Gynecol. (2003) [Pubmed]
  4. Role of SOCS2 in growth hormone actions. Turnley, A.M. Trends Endocrinol. Metab. (2005) [Pubmed]
  5. Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Machado, F.S., Johndrow, J.E., Esper, L., Dias, A., Bafica, A., Serhan, C.N., Aliberti, J. Nat. Med. (2006) [Pubmed]
  6. Suppressor of cytokine signaling-2: a growth hormone-inducible inhibitor of intestinal epithelial cell proliferation. Miller, M.E., Michaylira, C.Z., Simmons, J.G., Ney, D.M., Dahly, E.M., Heath, J.K., Lund, P.K. Gastroenterology (2004) [Pubmed]
  7. Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Leung, K.C., Doyle, N., Ballesteros, M., Sjogren, K., Watts, C.K., Low, T.H., Leong, G.M., Ross, R.J., Ho, K.K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Concentration-dependent collateral sensitivity of cisplatin-resistant gastric cancer cell sublines. Xu, H., Choi, S.M., An, C.S., Min, Y.D., Kim, K.C., Kim, K.J., Choi, C.H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  9. Identification of suppressors of cytokine signaling (SOCS) proteins in human gestational tissues: differential regulation is associated with the onset of labor. Blumenstein, M., Bowen-Shauver, J.M., Keelan, J.A., Mitchell, M.D. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  10. Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. Rico-Bautista, E., Flores-Morales, A., Fern??ndez-P??rez, L. Cytokine Growth Factor Rev. (2006) [Pubmed]
  11. Ultraviolet B radiation-mediated inhibition of interferon-gamma-induced keratinocyte activation is independent of interleukin-10 and other soluble mediators but associated with enhanced intracellular suppressors of cytokine-signaling expression. Friedrich, M., Holzmann, R., Sterry, W., Wolk, K., Truppel, A., Piazena, H., Schonbein, C., Sabat, R., Asadullah, K. J. Invest. Dermatol. (2003) [Pubmed]
  12. Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively. Yandava, C.N., Pillari, A., Drazen, J.M. Genomics (1999) [Pubmed]
  13. Preparation and expression of biologically active prolactin and growth hormone receptors and suppressor of cytokine signaling proteins 1, 2, 3, and 6 tagged with cyan and yellow fluorescent proteins. Ben-Yair, L., Slaaby, R., Herman, A., Cohen, Y., Biener, E., Moran, N., Yoshimura, A., Whittaker, J., De Meyts, P., Herman, B., Gertler, A. Protein Expr. Purif. (2002) [Pubmed]
  14. Human growth hormone induces SOCS3 and CIS mRNA increase in the hypothalamic neurons of hypophysectomized rats. Kasagi, Y., Tokita, R., Nakata, T., Imaki, T., Minami, S. Endocr. J. (2004) [Pubmed]
  15. Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. Dey, B.R., Spence, S.L., Nissley, P., Furlanetto, R.W. J. Biol. Chem. (1998) [Pubmed]
  16. Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese. Kato, H., Nomura, K., Osabe, D., Shinohara, S., Mizumori, O., Katashima, R., Iwasaki, S., Nishimura, K., Yoshino, M., Kobori, M., Ichiishi, E., Nakamura, N., Yoshikawa, T., Tanahashi, T., Keshavarz, P., Kunika, K., Moritani, M., Kudo, E., Tsugawa, K., Takata, Y., Hamada, D., Yasui, N., Miyamoto, T., Shiota, H., Inoue, H., Itakura, M. Genomics (2006) [Pubmed]
  17. Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo. Michaylira, C.Z., Simmons, J.G., Ramocki, N.M., Scull, B.P., McNaughton, K.K., Fuller, C.R., Lund, P.K. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  18. A complex interaction pattern of CIS and SOCS2 with the leptin receptor. Lavens, D., Montoye, T., Piessevaux, J., Zabeau, L., Vandekerckhove, J., Gevaert, K., Becker, W., Eyckerman, S., Tavernier, J. J. Cell. Sci. (2006) [Pubmed]
  19. Differential regulation of signaling pathways for insulin and insulin-like growth factor I. Lopaczynski, W. Acta Biochim. Pol. (1999) [Pubmed]
  20. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Dey, B.R., Furlanetto, R.W., Nissley, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  21. The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. Song, M.M., Shuai, K. J. Biol. Chem. (1998) [Pubmed]
  22. Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma. Marini, A., Mirmohammadsadegh, A., Nambiar, S., Gustrau, A., Ruzicka, T., Hengge, U.R. J. Invest. Dermatol. (2006) [Pubmed]
  23. Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines. Dogusan, Z., Hooghe-Peters, E.L., Berus, D., Velkeniers, B., Hooghe, R. J. Neuroimmunol. (2000) [Pubmed]
  24. Suppressor of cytokine signalling 2 (SOCS-2) expression in breast carcinoma. Farabegoli, F., Ceccarelli, C., Santini, D., Taffurelli, M. J. Clin. Pathol. (2005) [Pubmed]
  25. Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat. Wang, L., Zhang, Z., Zhang, R., Hafner, M.S., Wong, H.K., Jiao, Z., Chopp, M. Neuroreport (2004) [Pubmed]
  26. Skeletal muscle, cytokines, and oxidative stress in end-stage renal disease. Raj, D.S., Dominic, E.A., Pai, A., Osman, F., Morgan, M., Pickett, G., Shah, V.O., Ferrando, A., Moseley, P. Kidney Int. (2005) [Pubmed]
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