Socs3

Summary

Gene Symbol: Socs3
Description: suppressor of cytokine signaling 3
Alias: Cis3, Cish3, EF-10, Ef10, SSI-3, Ssi3, suppressor of cytokine signaling 3, CIS-3, E2a-Pbx1 target gene in fibroblasts 10, STAT-induced STAT inhibitor 3, cytokine inducible SH2-containing protein 3
Species: mouse
Products:     Socs3

Top Publications

  1. Brown R, Imran S, Belsham D, Ur E, Wilkinson M. Adipokine gene expression in a novel hypothalamic neuronal cell line: resistin-dependent regulation of fasting-induced adipose factor and SOCS-3. Neuroendocrinology. 2007;85:232-41 pubmed
    ..However, it remains to be determined whether these in vitro results can be translated to the control of adipokine expression in brain and adipose tissue. ..
  2. Sasaki A, Inagaki Ohara K, Yoshida T, Yamanaka A, Sasaki M, Yasukawa H, et al. The N-terminal truncated isoform of SOCS3 translated from an alternative initiation AUG codon under stress conditions is stable due to the lack of a major ubiquitination site, Lys-6. J Biol Chem. 2003;278:2432-6 pubmed
    The suppressor of cytokine signaling-3 (SOCS3/CIS-33/SSI-3) is an important negative regulator of cytokine signaling...
  3. Ogata H, Kobayashi T, Chinen T, Takaki H, Sanada T, Minoda Y, et al. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology. 2006;131:179-93 pubmed
    A recent study has suggested that the methylation silencing of the suppressor of cytokine signaling-3 (SOCS3), a negative regulator of interleukin-6-related cytokines, could be involved in hepatocellular carcinoma (HCC)...
  4. Lu Y, Fukuyama S, Yoshida R, Kobayashi T, Saeki K, Shiraishi H, et al. Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro-apoptotic. J Biol Chem. 2006;281:36683-90 pubmed
    ..In this report, we generated SOCS3-deficient murine embryonic fibroblasts (MEFs), in which STAT3 activation is extremely enhanced and prolonged...
  5. Ozawa Y, Nakao K, Shimazaki T, Shimmura S, Kurihara T, Ishida S, et al. SOCS3 is required to temporally fine-tune photoreceptor cell differentiation. Dev Biol. 2007;303:591-600 pubmed
    b>Suppressor of cytokine signaling 3 (SOCS3) is an intracellular, ligand-induced negative feedback modulator of STAT3 activation that acts during inflammation...
  6. Boyle K, Zhang J, Nicholson S, Trounson E, Babon J, McManus E, et al. Deletion of the SOCS box of suppressor of cytokine signaling 3 (SOCS3) in embryonic stem cells reveals SOCS box-dependent regulation of JAK but not STAT phosphorylation. Cell Signal. 2009;21:394-404 pubmed publisher
    The mechanism by which Suppressor of Cytokine Signaling-3 (SOCS3) negatively regulates cytokine signaling has been widely investigated using over-expression studies in cell lines and is thought to involve interactions with both the gp130 ..
  7. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, et al. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci U S A. 2002;99:13003-8 pubmed
    ..Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance. ..
  8. Kundu K, Dutta K, Nazmi A, Basu A. Japanese encephalitis virus infection modulates the expression of suppressors of cytokine signaling (SOCS) in macrophages: implications for the hosts' innate immune response. Cell Immunol. 2013;285:100-10 pubmed publisher
    ..On knocking down SOCS1 and SOCS3 we found a significant decrease in viral gene expression at an early time point, indicating the dysregulation of ..
  9. Kievit P, Howard J, Badman M, Balthasar N, Coppari R, Mori H, et al. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab. 2006;4:123-32 pubmed
    ..These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism. ..

More Information

Publications76

  1. Qasimi P, Ming Lum A, Ghanipour A, Ong C, Cox M, Ihle J, et al. Divergent mechanisms utilized by SOCS3 to mediate interleukin-10 inhibition of tumor necrosis factor alpha and nitric oxide production by macrophages. J Biol Chem. 2006;281:6316-24 pubmed
    ..The expression of SOCS3 (suppressor of cytokine signaling-3) has been shown to be induced by IL-10 in a STAT3-dependent manner...
  2. Hilton D, Richardson R, Alexander W, Viney E, Willson T, Sprigg N, et al. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci U S A. 1998;95:114-9 pubmed
    ..The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. The function of the WSB, SSB, and ASB protein families remains to be determined. ..
  3. Shi H, Tzameli I, Bjørbaek C, Flier J. Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. J Biol Chem. 2004;279:34733-40 pubmed
    ..We observed that several cytokines and hormones that induce insulin resistance also stimulate SOCS3 expression in 3T3-L1 adipocytes and that SOCS3 mRNA is increased in adipose tissue of obese/diabetic mice...
  4. Sachithanandan N, Fam B, Fynch S, Dzamko N, Watt M, Wormald S, et al. Liver-specific suppressor of cytokine signaling-3 deletion in mice enhances hepatic insulin sensitivity and lipogenesis resulting in fatty liver and obesity. Hepatology. 2010;52:1632-42 pubmed publisher
    ..The suppressor of cytokine signaling-3 (SOCS3) protein is increased in inflammation and is thought to contribute to the pathogenesis of insulin resistance by ..
  5. Sun R, Jaruga B, Kulkarni S, Sun H, Gao B. IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation by SOCS3. Biochem Biophys Res Commun. 2005;338:1943-9 pubmed
    The precise role of IL-6 in liver regeneration and hepatocyte proliferation is controversial and the role of SOCS3 in liver regeneration remains unknown...
  6. Yarwood S, Borland G, Sands W, Palmer T. Identification of CCAAT/enhancer-binding proteins as exchange protein activated by cAMP-activated transcription factors that mediate the induction of the SOCS-3 gene. J Biol Chem. 2008;283:6843-53 pubmed publisher
    ..In summary, our findings constitute the first description of an EPAC-C/EBP pathway that can control cAMP-mediated changes in gene expression independently of protein kinase A. ..
  7. Matarazzo V, Schaller F, Nedelec E, Benani A, Penicaud L, Muscatelli F, et al. Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci. 2012;32:17097-107 pubmed publisher
    ..One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation...
  8. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med. 2006;12:829-34 pubmed
    ..deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3(-/-), Nes-Socs3(-/-))...
  9. Barclay J, Anderson S, Waters M, Curlewis J. Regulation of suppressor of cytokine signaling 3 (SOC3) by growth hormone in pro-B cells. Mol Endocrinol. 2007;21:2503-15 pubmed
    b>Suppressor of cytokine signaling 3 (SOCS3) is expressed by lymphoid cells and can modulate the sensitivity of these cells to cytokine stimulation through inhibition of Janus kinase (JAK)/signal transducers and activators of transcription (..
  10. Ueki K, Kondo T, Tseng Y, Kahn C. Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. Proc Natl Acad Sci U S A. 2004;101:10422-7 pubmed
    ..Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling. ..
  11. El Kasmi K, Holst J, Coffre M, Mielke L, de Pauw A, Lhocine N, et al. General nature of the STAT3-activated anti-inflammatory response. J Immunol. 2006;177:7880-8 pubmed
    ..We conclude that the AIR is a generic cytokine signaling pathway dependent on STAT3 but not unique to the IL-10R. ..
  12. Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A. CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J Biol Chem. 2000;275:29338-47 pubmed
    The cytokine-inducible SH2 protein-3 (CIS3/SOCS-3/SSI-3) has been shown to inhibit the JAK/STAT pathway and act as a negative regulator of fetal liver erythropoiesis...
  13. Yu C, Mahdi R, Ebong S, Vistica B, Gery I, Egwuagu C. Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells. J Biol Chem. 2003;278:29752-9 pubmed
    ..We show that SOCS1, SOCS2, SOCS3, CIS (cytokine-induced SH2 protein) genes are constitutively expressed in naïve T-helper cells, with SOCS3 being ..
  14. Luckett Chastain L, Ihnat M, Mickle Kawar B, GALLUCCI R. SOCS3 modulates interleukin-6R signaling preference in dermal fibroblasts. J Interferon Cytokine Res. 2012;32:207-15 pubmed publisher
    ..Dermal fibroblasts isolated from IL-6KO mice were pretreated with specific ERK or STAT3 chemical inhibitors or SOCS3 specific siRNA and treated with rmIL-6...
  15. Moriwaki A, Inoue H, Nakano T, Matsunaga Y, Matsuno Y, Matsumoto T, et al. T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma. Am J Respir Cell Mol Biol. 2011;44:448-55 pubmed publisher
    ..Mice that lack SOCS3 in T cells by crossing SOCS3-floxed mice with Lck-Cre-transgenic mice have reduced allergen-induced eosinophilia ..
  16. Croker B, Krebs D, Zhang J, Wormald S, Willson T, Stanley E, et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003;4:540-5 pubmed
    ..To examine whether SOCS3 is involved in regulating this signaling, we have used conditional gene targeting to generate mice lacking Socs3 ..
  17. Caruso R, Stolfi C, Sarra M, Rizzo A, Fantini M, Pallone F, et al. Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3. Blood. 2009;113:3512-9 pubmed publisher
    ..These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications. ..
  18. Shi H, Cave B, Inouye K, Bjørbaek C, Flier J. Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistance. Diabetes. 2006;55:699-707 pubmed
    ..Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, ..
  19. Miao T, Wu D, Zhang Y, Bo X, Xiao F, Zhang X, et al. SOCS3 suppresses AP-1 transcriptional activity in neuroblastoma cells through inhibition of c-Jun N-terminal kinase. Mol Cell Neurosci. 2008;37:367-75 pubmed
    ..Overexpression of SOCS3 (suppressor of cytokine signaling) inhibited and mutant SOCS3 (with an inactivating point mutation in amino acid ..
  20. Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, et al. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003;9:1047-54 pubmed
    ..In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development...
  21. Kimura A, Kinjyo I, Matsumura Y, Mori H, Mashima R, Harada M, et al. SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte colony-stimulating factor receptor signaling. J Biol Chem. 2004;279:6905-10 pubmed
    The suppressor of cytokine signaling-3 (SOCS3/CIS3) has been shown to be an important negative regulator of cytokines, especially cytokines that activate STAT3...
  22. Ortiz Muñoz G, Martin Ventura J, Hernandez Vargas P, Mallavia B, Lopez Parra V, Lopez Franco O, et al. Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:525-31 pubmed publisher
    ..Immunohistochemistry in human plaques revealed a high expression of SOCS1 and SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory region of the shoulders, when compared ..
  23. Matsumura Y, Kobayashi T, Ichiyama K, Yoshida R, Hashimoto M, Takimoto T, et al. Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J Immunol. 2007;179:2170-9 pubmed
    ..b>SOCS3(-/-) DCs expressed lower levels of class II MHC, CD40, CD86, and IL-12 than wild-type (WT)-DCs both in vitro and ..
  24. Babon J, Sabo J, Soetopo A, Yao S, Bailey M, Zhang J, et al. The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase. J Mol Biol. 2008;381:928-40 pubmed publisher
    Suppressor of cytokine signalling 3 (SOCS3) is responsible for regulating the cellular response to a variety of cytokines, including interleukin 6 and leukaemia inhibitory factor...
  25. Lang R, Pauleau A, Parganas E, Takahashi Y, Mages J, Ihle J, et al. SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol. 2003;4:546-50 pubmed
    ..b>SOCS3 is upregulated by several signals in macrophages and has been implicated as a regulator of various signaling ..
  26. Marine J, McKay C, Wang D, Topham D, Parganas E, Nakajima H, et al. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999;98:617-27 pubmed
    b>SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling...
  27. Hill G, Kuns R, Raffelt N, Don A, Olver S, Markey K, et al. SOCS3 regulates graft-versus-host disease. Blood. 2010;116:287-96 pubmed publisher
    Suppressor of cytokine signaling-3 (SOCS3) is the main intracellular regulator of signaling by granulocyte colony-stimulating factor, an immune-modulatory cytokine used to mobilize stem cells for transplantation...
  28. Steppan C, Wang J, Whiteman E, Birnbaum M, Lazar M. Activation of SOCS-3 by resistin. Mol Cell Biol. 2005;25:1569-75 pubmed
    ..Remarkably, resistin treatment markedly induces the gene expression of suppressor of cytokine signaling 3 (SOCS-3), a known inhibitor of insulin signaling...
  29. Zhang R, Dhillon H, Yin H, Yoshimura A, Lowell B, Maratos Flier E, et al. Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology. 2008;149:5654-61 pubmed publisher
    b>Suppressor of cytokine signaling 3 (Socs3) has been identified as a mediator of central leptin resistance, but the identity of specific neurons in which Socs3 acts to suppress leptin signaling remains elusive...
  30. Nicholson S, Willson T, Farley A, Starr R, Zhang J, Baca M, et al. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 1999;18:375-85 pubmed
    ..Thus, although inhibition of signaling by SOCS-1 and SOCS-3 requires both the SH2 and N-terminal domains, their mechanisms of action appear to be biochemically different. ..
  31. Baetz A, Frey M, Heeg K, Dalpke A. Suppressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like receptor signaling in innate immune cells. J Biol Chem. 2004;279:54708-15 pubmed
    ..Thus, our data suggest that SOCS proteins induced by TLR stimulation limit the extent of TLR signaling by inhibiting type I IFN signaling but not the main NF kappa B pathway. ..
  32. Mansfield K, Johnson N, Cosby S, Solomon T, Fooks A. Transcriptional upregulation of SOCS 1 and suppressors of cytokine signaling 3 mRNA in the absence of suppressors of cytokine signaling 2 mRNA after infection with West Nile virus or tick-borne encephalitis virus. Vector Borne Zoonotic Dis. 2010;10:649-53 pubmed publisher
  33. Egwuagu C, Yu C, Zhang M, Mahdi R, Kim S, Gery I. Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance. J Immunol. 2002;168:3181-7 pubmed
    ..We show here that CD4(+) naive T cells constitutively express low levels of SOCS1, SOCS2, and SOCS3 mRNAs...
  34. Croker B, Mielke L, Wormald S, Metcalf D, Kiu H, Alexander W, et al. Socs3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiation. Exp Hematol. 2008;36:786-98 pubmed publisher
    ..and are both negatively regulated by the inducible intracellular protein suppressor of cytokine signaling-3 (Socs3)...
  35. Starr R, Willson T, Viney E, Murray L, Rayner J, Jenkins B, et al. A family of cytokine-inducible inhibitors of signalling. Nature. 1997;387:917-21 pubmed
    ..Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction. ..
  36. Auernhammer C, Bousquet C, Melmed S. Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. Proc Natl Acad Sci U S A. 1999;96:6964-9 pubmed
    ..These results demonstrate a mechanism for corticotroph plasticity with rapid "on" and "off" ACTH induction in response to neuro-immuno-endocrine stimuli, such as LIF. ..
  37. Berlato C, Cassatella M, Kinjyo I, Gatto L, Yoshimura A, Bazzoni F. Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory effects of IL-10 on lipopolysaccharide-induced macrophage activation. J Immunol. 2002;168:6404-11 pubmed
    Previous studies have shown that IL-10 can induce the expression of the suppressor of cytokine signaling 3 (SOCS-3) mRNA in human monocytes and neutrophils, suggesting that the capacity of IL-10 to inhibit the expression of LPS-inducible ..
  38. Polizzotto M, Bartlett P, Turnley A. Expression of "suppressor of cytokine signalling" (SOCS) genes in the developing and adult mouse nervous system. J Comp Neurol. 2000;423:348-58 pubmed
    ..Its expression pattern indicated that SOCS-2 was expressed exclusively in neurons and that it was switched on developmentally at the time of neuronal differentiation. ..
  39. Rui L, Yuan M, Frantz D, Shoelson S, White M. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394-8 pubmed
    ..Inflammation induces the expression of SOCS proteins. We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation...
  40. Senn J, Klover P, Nowak I, Zimmers T, Koniaris L, Furlanetto R, et al. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem. 2003;278:13740-6 pubmed
    ..These data suggest that induction of SOCS-3 in liver may be an important mechanism of IL-6-mediated insulin resistance. ..
  41. Babon J, Sabo J, Zhang J, Nicola N, Norton R. The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression. J Mol Biol. 2009;387:162-74 pubmed
  42. Wong P, Egan P, Croker B, O Donnell K, Sims N, Drake S, et al. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest. 2006;116:1571-81 pubmed
    ..The generation of Socs3(-/Delta vav) mice, which lack SOCS-3 in the hematopoietic and endothelial cell compartment, allowed us to explore ..
  43. Sun F, Park K, Belin S, Wang D, Lu T, Chen G, et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 2011;480:372-5 pubmed publisher
    ..PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in ..
  44. Yang X, Schaper F, Teubner A, Lammert F, Heinrich P, Matern S, et al. Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo. J Hepatol. 2005;43:704-10 pubmed
    ..However, several signaling pathways converge on SOCS3: SOCS3 can be induced by other mediators in vitro, and it does not exclusively inhibit IL-6 signaling...
  45. Narayana Y, Balaji K. NOTCH1 up-regulation and signaling involved in Mycobacterium bovis BCG-induced SOCS3 expression in macrophages. J Biol Chem. 2008;283:12501-11 pubmed publisher
    ..is known about the early receptor proximal signaling mechanisms underlying mycobacteria-mediated induction of SOCS3. We demonstrate here for the first time that M...
  46. Howard J, Cave B, Oksanen L, Tzameli I, Bjørbaek C, Flier J. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med. 2004;10:734-8 pubmed
    ..We have previously identified suppressor of cytokine signaling-3 (Socs3) as a leptin-induced negative regulator of leptin receptor signaling and potential mediator of leptin resistance...
  47. Lehmann U, Schmitz J, Weissenbach M, Sobota R, Hortner M, Friederichs K, et al. SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130. J Biol Chem. 2003;278:661-71 pubmed
    ..We recently observed that the suppressor of cytokine-signaling SOCS3 also acts through the tyrosine motif 759 of gp130...
  48. Akhtar L, Qin H, Muldowney M, Yanagisawa L, Kutsch O, Clements J, et al. Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages. J Immunol. 2010;185:2393-404 pubmed publisher
    ..We found that SOCS3 is elevated in an in vivo SIV/macaque model of HAD and that the pattern of expression correlates with recurrence ..
  49. Brown R, Imran S, Wilkinson M. Lipopolysaccharide (LPS) stimulates adipokine and socs3 gene expression in mouse brain and pituitary gland in vivo, and in N-1 hypothalamic neurons in vitro. J Neuroimmunol. 2009;209:96-103 pubmed publisher
  50. Croker B, Metcalf D, Robb L, Wei W, Mifsud S, Dirago L, et al. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity. 2004;20:153-65 pubmed
    To determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the regulation of hematopoietic growth factor signaling generally, and of G-CSF-induced cellular responses specifically, we created mice in which the Socs3 gene ..
  51. Qin H, Niyongere S, Lee S, Baker B, Benveniste E. Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes. J Immunol. 2008;181:3167-76 pubmed
    ..These results indicate that IFN-beta induces SOCS-1 and SOCS-3 in primary astrocytes to attenuate its own chemokine-related inflammation in the CNS. ..
  52. Qin H, Yeh W, De Sarno P, Holdbrooks A, Liu Y, Muldowney M, et al. Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation. Proc Natl Acad Sci U S A. 2012;109:5004-9 pubmed publisher
    Suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of the JAK/STAT pathway. SOCS3 has a crucial role in inhibiting STAT3 activation, cytokine signaling, and inflammatory gene expression in macrophages/microglia...
  53. Zhu B, Ishida Y, Robinson G, Pacher Zavisin M, Yoshimura A, Murphy P, et al. SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. J Invest Dermatol. 2008;128:1821-9 pubmed publisher
    ..b>Socs3 alleles flanked by loxP sites were deleted in mice with either an MMTV-Cre or K5-Cre transgene...
  54. Matsumoto A, Seki Y, Watanabe R, Hayashi K, Johnston J, Harada Y, et al. A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. J Exp Med. 2003;197:425-36 pubmed
    ..However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T ..
  55. Babon J, Yao S, DeSouza D, Harrison C, Fabri L, Liepinsh E, et al. Secondary structure assignment of mouse SOCS3 by NMR defines the domain boundaries and identifies an unstructured insertion in the SH2 domain. FEBS J. 2005;272:6120-30 pubmed
    b>SOCS3 is a negative regulator of cytokine signalling that inhibits Janus kinase-signal transduction and activator of transcription (JAK-STAT) mediated signal tranduction by binding to phosphorylated tyrosine residues on intracellular ..
  56. Qin H, Roberts K, Niyongere S, Cong Y, Elson C, Benveniste E. Molecular mechanism of lipopolysaccharide-induced SOCS-3 gene expression in macrophages and microglia. J Immunol. 2007;179:5966-76 pubmed
  57. Metlakunta A, Sahu M, Yasukawa H, Dhillon S, Belsham D, Yoshimura A, et al. Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling. Am J Physiol Regul Integr Comp Physiol. 2011;300:R1185-93 pubmed publisher
    Suppressor of cytokine signaling-3 (SOCS3) is thought to be involved in the development of central leptin resistance and obesity by inhibiting STAT3 pathway...
  58. Chen Z, Laurence A, Kanno Y, Pacher Zavisin M, Zhu B, Tato C, et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A. 2006;103:8137-42 pubmed
    ..We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, ..
  59. Gao H, Hoesel L, Guo R, Rancilio N, Sarma J, Ward P. Adenoviral-mediated overexpression of SOCS3 enhances IgG immune complex-induced acute lung injury. J Immunol. 2006;177:612-20 pubmed
    ..Recently, suppressor of cytokine signaling 3 (SOCS3) has been shown to be a key negative regulator of IL-6/gp130/Jak/STAT3 signal transduction...
  60. Sommer U, Schmid C, Sobota R, Lehmann U, Stevenson N, Johnston J, et al. Mechanisms of SOCS3 phosphorylation upon interleukin-6 stimulation. Contributions of Src- and receptor-tyrosine kinases. J Biol Chem. 2005;280:31478-88 pubmed
    The suppressors of cytokine signaling (SOCS) are negative feedback inhibitors of cytokine signal transduction. SOCS3 is a key negative regulator of interleuking-6 (IL-6) signal transduction...
  61. Lebrun P, Cognard E, Bellon Paul R, Gontard P, Filloux C, Jehl Pietri C, et al. Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice. Diabetologia. 2009;52:2201-12 pubmed publisher
    ..In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity. ..
  62. Takahashi Y, Carpino N, Cross J, Torres M, Parganas E, Ihle J. SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation. EMBO J. 2003;22:372-84 pubmed
    b>Suppressor of cytokine signaling 3 (SOCS3) binds cytokine receptors and thereby suppresses cytokine signaling...
  63. Wormald S, Zhang J, Krebs D, Mielke L, Silver J, Alexander W, et al. The comparative roles of suppressor of cytokine signaling-1 and -3 in the inhibition and desensitization of cytokine signaling. J Biol Chem. 2006;281:11135-43 pubmed
    ..STAT3 tyrosine phosphorylation was bi-phasic in response to continuous IL-6 signaling. In macrophages lacking Socs3, however, continuous IL-6 signaling induced uniformly high levels of STAT3 tyrosine phosphorylation, and early IL-..
  64. Spangenburg E. SOCS-3 induces myoblast differentiation. J Biol Chem. 2005;280:10749-58 pubmed
    ..These data suggest that IGF-I induces myoblast differentiation, in part, by increasing SOCS-3 expression. ..
  65. Jo D, Liu D, Yao S, Collins R, Hawiger J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat Med. 2005;11:892-8 pubmed
    ..B (SEB) and lipopolysaccharide (LPS), or the lectin concanavalin A (ConA), suggesting that physiologic levels of SOCS3 are insufficient to stem proinflammatory signaling under pathogenic circumstances...
  66. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, et al. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med. 2004;10:739-43 pubmed
    ..In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance...
  67. Bergamin E, Wu J, Hubbard S. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Structure. 2006;14:1285-92 pubmed
    ..The N-terminal region in SOCS1 and SOCS3 includes the so-called kinase inhibitory region that has been shown to inhibit the catalytic activity of JAK2...