Genomes and Genes
Gene Symbol: Socs2
Description: suppressor of cytokine signaling 2
Alias: 8030460M17, AI527257, AW108012, CIS2, Cish2, D130043N08Rik, JAB, SOCS-2, SSI-2, suppressor of cytokine signaling 2, CIS-2, STAT-induced STAT inhibitor 2, cytokine inducible SH2-containing protein 2, cytokine-inducible SH2 protein 2
- Pass C, Macrae V, Huesa C, Faisal Ahmed S, Farquharson C. SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis. J Bone Miner Res. 2012;27:1055-66 pubmed publisherSuppressor of Cytokine Signaling-2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway...
- Uyttendaele I, Lemmens I, Verhee A, de Smet A, Vandekerckhove J, Lavens D, et al. Mammalian protein-protein interaction trap (MAPPIT) analysis of STAT5, CIS, and SOCS2 interactions with the growth hormone receptor. Mol Endocrinol. 2007;21:2821-31 pubmed publisher..of cytokine signaling cytokine-inducible Src-homology 2 (SH2)-containing protein (CIS) and suppressor of cytokine signaling 2 (SOCS2). Y534, Y566, and Y627 are the major recruitment sites for STAT5...
- Horvat S, Medrano J. Interval mapping of high growth (hg), a major locus that increases weight gain in mice. Genetics. 1995;139:1737-48 pubmed..The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals. ..
- Greenhalgh C, Rico Bautista E, Lorentzon M, Thaus A, Morgan P, Willson T, et al. SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest. 2005;115:397-406 pubmedMice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase in mature body size...
- Jegalian A, Wu H. Differential roles of SOCS family members in EpoR signal transduction. J Interferon Cytokine Res. 2002;22:853-60 pubmed..EpoR mutants and thereby activate only subsets of signaling cascades, we demonstrate that induction of SOCS1, SOCS2, SOCS3, and cytokine-inducible SH2-containing protein (CIS) in response to EPO stimulation appears to depend on ..
- Greenhalgh C, Bertolino P, Asa S, Metcalf D, Corbin J, Adams T, et al. Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b). Mol Endocrinol. 2002;16:1394-406 pubmed..Furthermore, the deletion of SOCS-2 from mice also lacking signal transducer and activator of transcription 5b had little effect on growth, suggesting that the action of SOCS-2 may be the regulation of the GH signaling pathway. ..
- Rico Bautista E, Greenhalgh C, Tollet Egnell P, Hilton D, Alexander W, Norstedt G, et al. Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects. Mol Endocrinol. 2005;19:781-93 pubmedSuppressor of cytokine signaling-2 (SOCS2)-deficient (SOCS2-/-) mice grow significantly larger than their littermates, suggesting that SOCS2 is important in the negative regulation of the actions of GH and/or IGF-I...
- Horvat S, Medrano J. Lack of Socs2 expression causes the high-growth phenotype in mice. Genomics. 2001;72:209-12 pubmed..We conclude that hg is an allele of the suppressor of cytokine signaling 2 (Socs2), a member of a family of regulators of cytokine signal transduction...
- 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. ..
- 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
- Wong M, Islas Trejo A, Medrano J. Structural characterization of the mouse high growth deletion and discovery of a novel fusion transcript between suppressor of cytokine signaling-2 (Socs-2) and viral encoded semaphorin receptor (Plexin C1). Gene. 2002;299:153-63 pubmed..Genomic comparisons of the mouse and human sequence were used to verify the sequence assembly. ..
- Turnley A, Faux C, Rietze R, Coonan J, Bartlett P. Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. Nat Neurosci. 2002;5:1155-62 pubmed..We found that expression of SOCS2, an intracellular regulator of cytokine signaling, was restricted to mouse progenitor cells and neurons in ..
- Lavens D, Montoye T, Piessevaux J, Zabeau L, Vandekerckhove J, Gevaert K, et al. A complex interaction pattern of CIS and SOCS2 with the leptin receptor. J Cell Sci. 2006;119:2214-24 pubmed..Here, we show that CIS (cytokine-inducible SH2 protein) and SOCS2 can also interact with the leptin receptor...
- Harris J, Stanford P, Sutherland K, Oakes S, Naylor M, Robertson F, et al. Socs2 and elf5 mediate prolactin-induced mammary gland development. Mol Endocrinol. 2006;20:1177-87 pubmed..prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5)...
- Corva P, Horvat S, Medrano J. Quantitative trait loci affecting growth in high growth (hg) mice. Mamm Genome. 2001;12:284-90 pubmed
- Rocha Resende C, Guedes de Jesus I, Roman Campos D, Miranda A, Alves F, Resende R, et al. Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca2+ levels. Am J Physiol Cell Physiol. 2017;312:C478-C486 pubmed publisher..We investigated the consequences of SOCS2 ablation for leukemia inhibitory factor (LIF)-induced enhancement of intracellular Ca2+ ([Ca2+Iglesias Gato D, Chuan Y, Wikstrom P, Augsten S, Jiang N, Niu Y, et al. SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer. Carcinogenesis. 2014;35:24-33 pubmed publisher..In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross talk between androgens and GH signals in the prostate and its ..Knosp C, Carroll H, Elliott J, Saunders S, Nel H, Amu S, et al. SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses. J Exp Med. 2011;208:1523-31 pubmed publisher..We report that SOCS2(-/-) CD4(+) T cells show markedly enhanced Th2 differentiation...Ransome M, Turnley A. Growth hormone signaling and hippocampal neurogenesis: insights from genetic models. Hippocampus. 2008;18:1034-50 pubmed publisher..Furthermore, voluntary running increased AHN in WT, SOCS-2 Tg, and serum-IGF-1-deficient GH-R-/- mice. ..Jiao Y, Rieck S, Le Lay J, Kaestner K. CISH has no non-redundant functions in glucose homeostasis or beta cell proliferation during pregnancy in mice. Diabetologia. 2013;56:2435-45 pubmed publisher..The p-STAT5 protein level was the same in Cish mutant and control mice. Socs2 gene expression was higher in Cish mutant than control mice at pregnancy day 9.5...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. ..Kato H, Nomura K, Osabe D, Shinohara S, Mizumori O, Katashima R, et al. Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese. Genomics. 2006;87:446-58 pubmed..6 kb of genomic DNA that includes the entire SOCS2 gene...Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, et al. Cloning and characterization of novel CIS family genes. Biochem Biophys Res Commun. 1997;239:439-46 pubmed..Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search...Scott H, Stebbing M, Walters C, McLenachan S, Ransome M, Nichols N, et al. Differential effects of SOCS2 on neuronal differentiation and morphology. Brain Res. 2006;1067:138-45 pubmed..Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of Growth Hormone (GH) signaling that is expressed in neural stem cells and neurons ..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..Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis. ..Uren R, Turbic A, Wong A, Klein R, Murray S, Turnley A. A novel role of suppressor of cytokine signaling-2 in the regulation of TrkA neurotrophin receptor biology. J Neurochem. 2014;129:614-27 pubmed publisherSuppressor of cytokine signaling-2 (SOCS2) is a regulator of intracellular responses to growth factors and cytokines...Corva P, Medrano J. Diet effects on weight gain and body composition in high growth (hg/hg) mice. Physiol Genomics. 2000;3:17-23 pubmed..These results show that the effects of hg on growth are modulated by diet composition. Therefore, this mutation could be a valuable model with which to study the genetic and nutritional aspects of overgrowth disorders...Masuzaki R, Zhao S, Valerius M, Tsugawa D, Oya Y, Ray K, et al. SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration. J Biol Chem. 2016;291:3346-58 pubmed publisher..A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial ..Boverhof D, Tam E, Harney A, Crawford R, Kaminski N, Zacharewski T. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. Mol Pharmacol. 2004;66:1662-70 pubmed..One transcript that was significantly induced by TCDD was suppressor of cytokine signaling 2 (Socs2)...Bradford G. Growth and reproduction in mice selected for rapid body weight gain. Genetics. 1971;69:499-512 pubmedRansome M, Goldshmit Y, Bartlett P, Waters M, Turnley A. Comparative analysis of CNS populations in knockout mice with altered growth hormone responsiveness. Eur J Neurosci. 2004;19:2069-79 pubmed..GH) inhibits neuronal differentiation and that this process is blocked by suppressor of cytokine signalling-2 (SOCS2)...Horvat S, Medrano J. Fine genetic mapping of the region surrounding the high growth (hg) locus in mouse chromosome 10: targeting random amplified polymorphic DNA (RAPD) markers. Mamm Genome. 1996;7:312-4 pubmedGan L, Liu Z, Zhang Z, Yang X, Liu J, Sun C. SOCS2 inhibited mitochondria biogenesis via inhibiting p38 MAPK/ATF2 pathway in C2C12 cells. Mol Biol Rep. 2014;41:627-37 pubmed publisherIn order to investigate the mechanism of suppressor of cytokine signaling 2 (SOCS2) on mitochondrial biogenesis, RNA interference and over-expression plasmid vectors of SOCS2 were used to transfect murine skeletal muscle C2C12 cells...Alexander W, Starr R, Fenner J, Scott C, Handman E, Sprigg N, et al. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell. 1999;98:597-608 pubmed..Our data indicate that SOCS1 is a key modulator of IFNgamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses. ..Frohman L. New insights into the regulation of somatotrope function using genetic and transgenic models. Metabolism. 1996;45:1-3 pubmed..They may provide insights into our understanding of human GH secretory disorders...Summers P, Medrano J. Morphometric analysis of skeletal muscle growth in the high growth mouse. Growth Dev Aging. 1994;58:135-48 pubmedDobie R, MacRae V, Huesa C, van t Hof R, Ahmed S, Farquharson C. Direct stimulation of bone mass by increased GH signalling in the osteoblasts of Socs2-/- mice. J Endocrinol. 2014;223:93-106 pubmed publisherThe suppressor of cytokine signalling (Socs2(-/-))-knockout mouse is characterised by an overgrowth phenotype due to enhanced GH signalling...Vitali C, Bassani C, Chiodoni C, Fellini E, Guarnotta C, Miotti S, et al. SOCS2 Controls Proliferation and Stemness of Hematopoietic Cells under Stress Conditions and Its Deregulation Marks Unfavorable Acute Leukemias. Cancer Res. 2015;75:2387-99 pubmed publisher..b>SOCS2, a feedback inhibitor of JAK-STAT pathways, is expressed in most primitive HSC and is upregulated in response to ..Legrand J, Roy E, Ellis J, Francois M, Brooks A, Khosrotehrani K. STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction. J Invest Dermatol. 2016;136:1781-1791 pubmed publisher..This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle...Nirschl C, Suárez Fariñas M, Izar B, Prakadan S, Dannenfelser R, Tirosh I, et al. IFN?-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Cell. 2017;170:127-141.e15 pubmed publisher..Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and ..Ouyang X, Fujimoto M, Nakagawa R, Serada S, Tanaka T, Nomura S, et al. SOCS-2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cells. J Cell Physiol. 2006;207:428-36 pubmedDilts R, Famula T, Bradford G. Ovulation rate and pre- and postimplantation survival in mice with a major gene for rapid postweaning gain. J Anim Sci. 1991;69:3590-6 pubmedCalvert C, Famula T, Bernier J, Khalaf N, Bradford G. Efficiency of growth in mice with a major gene for rapid postweaning gain. J Anim Sci. 1986;62:77-85 pubmed..The results demonstrated that hg influences growth in growth-neutral and growth-selected backgrounds. The gene also alters energy metabolism by increasing energetic efficiency of growth and(or) decreasing maintenance energy requirement. ..Fruchtman S, Simmons J, Michaylira C, Miller M, Greenhalgh C, Ney D, et al. Suppressor of cytokine signaling-2 modulates the fibrogenic actions of GH and IGF-I in intestinal mesenchymal cells. Am J Physiol Gastrointest Liver Physiol. 2005;289:G342-50 pubmedLebrun P, Cognard E, Gontard P, Bellon Paul R, Filloux C, Berthault M, et al. The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion. Diabetologia. 2010;53:1935-46 pubmed publisher..SOCS3 have been involved in immune and inflammatory processes, respectively, in beta cells, nothing is known about SOCS2 implication in the pancreas...Michaylira C, Ramocki N, Simmons J, Tanner C, McNaughton K, Woosley J, et al. Haplotype insufficiency for suppressor of cytokine signaling-2 enhances intestinal growth and promotes polyp formation in growth hormone-transgenic mice. Endocrinology. 2006;147:1632-41 pubmed..Suppressor of cytokine signaling-2 (SOCS2) limits GH action on body and organ growth, but its role in GH action on intestine is unknown...Dobie R, Ahmed S, Staines K, Pass C, Jasim S, Macrae V, et al. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1. J Cell Physiol. 2015;230:2796-806 pubmed publisher..Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels...Eberle M, Dalpke A. Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses. J Immunol. 2012;188:5644-54 pubmed publisher..Our results show that SOCS1 is expressed via a new, NF-?B-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming. ..Alkharusi A, Mirecki Garrido M, Ma Z, Zadjali F, Flores Morales A, NystrÃ¶m T, et al. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice. Horm Mol Biol Clin Investig. 2016;26:67-76 pubmed publisher..Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity...Lindeman G, Wittlin S, Lada H, Naylor M, Santamaria M, Zhang J, et al. SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice. Genes Dev. 2001;15:1631-6 pubmed..These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition. ..Yeste A, Takenaka M, Mascanfroni I, Nadeau M, Kenison J, Patel B, et al. Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci Signal. 2016;9:ra61 pubmed publisher..The induction of a tolerogenic phenotype in DCs by NPs was mediated by the AhR-dependent induction of Socs2, which resulted in inhibition of nuclear factor ÎºB activation and proinflammatory cytokine production (..Summers P, Medrano J. Delayed myogenesis associated with muscle fiber hyperplasia in high-growth mice. Proc Soc Exp Biol Med. 1997;214:380-5 pubmed..Delayed fusion of high-growth myoblasts may allow an increase in the muscle stem cell population, resulting in fiber hyperplasia at birth. ..Marine J, Topham D, McKay C, Wang D, Parganas E, Stravopodis D, et al. SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell. 1999;98:609-16 pubmed..Introducing a RAG2 or IFNgamma deficiency eliminates lethality. The results demonstrate that lymphocytes are critical to SOCS1-associated perinatal lethality and implicate SOCS1 in lymphocyte differentiation or regulation. ..Posselt G, Schwarz H, Duschl A, Horejs Hoeck J. Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced activation in human monocyte-derived dendritic cells. J Immunol. 2011;187:2875-84 pubmed publisher..Essential roles in DC function have been assigned to SOCS1 and SOCS3. In this article, we show that SOCS2 also is involved in DC regulation...Reiser K, Summers P, Medrano J, Rucker R, Last J, McDonald R. Effects of elevated circulating IGF-1 on the extracellular matrix in "high-growth" C57BL/6J mice. Am J Physiol. 1996;271:R696-703 pubmedRansome M, Turnley A. Analysis of neuronal subpopulations in mice over-expressing suppressor of cytokine signaling-2. Neuroscience. 2005;132:673-87 pubmed..Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of cytokine signaling that blocks the inhibitory effects of growth hormone on ..Esper L, Roman Campos D, Lara A, Brant F, Castro L, Barroso A, et al. Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease. Am J Pathol. 2012;181:130-40 pubmed publisher..b>Suppressor of cytokine signaling 2 (SOCS2) is a regulator of immune responses and may therefore participate in the pathogenesis of T...Zadjali F, Santana Farre R, Vesterlund M, Carow B, Mirecki Garrido M, Hernandez Hernandez I, et al. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J. 2012;26:3282-91 pubmed publisherHepatic steatosis is a prominent feature in patients with growth hormone (GH) deficiency. The ubiquitin ligase SOCS2 attenuates hepatic GH signaling by inhibiting the Janus kinase 2 (JAK2)-signal transducer and activator of transcription ..Zeng X, Willi M, Shin H, Hennighausen L, Wang C. Lineage-Specific and Non-specific Cytokine-Sensing Genes Respond Differentially to the Master Regulator STAT5. Cell Rep. 2016;17:3333-3346 pubmed publisher..To address this, we focused on Socs2, a widely expressed cytokine-sensing gene...Basrai H, Turbic A, Christie K, Turnley A. Suppressor of Cytokine Signalling 2 (SOCS2) Regulates Numbers of Mature Newborn Adult Hippocampal Neurons and Their Dendritic Spine Maturation. Cell Mol Neurobiol. 2017;37:899-909 pubmed publisherOverexpression of suppressor of cytokine signalling 2 (SOCS2) has been shown to promote hippocampal neurogenesis in vivo and promote neurite outgrowth of neurons in vitro...Galic S, Sachithanandan N, Kay T, Steinberg G. Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity. Biochem J. 2014;461:177-88 pubmed publisher..Lastly, we discuss the important findings from SOCS whole-body and tissue-specific null mice, which implicate an important role for these proteins in controlling insulin action and glucose homoeostasis in obesity. ..Aparecida Silva Barbosa A, Freitas Versiani A, Fonseca da Cunha Sousa L, Silva de Miranda A, Gasparini M, Brant F, et al. Role of the suppressor of cytokine signaling 2 (SOCS2) during meningoencephalitis caused by Bovine herpesvirus 5 (BoHV-5). Comp Immunol Microbiol Infect Dis. 2016;47:26-31 pubmed publisher..caused by Bovine herpesvirus 5 (BoHV-5) was evaluated by intracranial infection in C57BL/6 wild-type mice (WT) and SOCS2 deficient mice (SOCS2(-/-)). Both infected groups presented weight loss, ruffled fur and hunched posture...Montoye T, Lemmens I, Catteeuw D, Eyckerman S, Tavernier J. A systematic scan of interactions with tyrosine motifs in the erythropoietin receptor using a mammalian 2-hybrid approach. Blood. 2005;105:4264-71 pubmed..molecules, including cytokine-inducible SH2-containing protein (CIS), suppressor of cytokine signaling-2 (SOCS2), phosphatidylinositol 3'-kinase (PI3-K), phospholipase C-gamma (PLC-gamma), and signal transducer and activator ..Bradford G. Selection for litter size in mice in the presence and absence of gonadotropin treatment. Genetics. 1968;58:283-95 pubmedPiper E, Chen Y, Moran C. Assignment of suppressor of cytokine signalling-2 (SOCS2) to porcine chromosome 5 with radiation hybrids. Cytogenet Genome Res. 2005;111:96 pubmedda Cunha Sousa L, Rachid M, Lima G, de Miranda A, de Carvalho Vilela M, Lacerda Queiroz N, et al. Suppressor of cytokine signaling 2 (SOCS2) contributes to encephalitis in a model of Herpes infection in mice. Brain Res Bull. 2016;127:164-170 pubmed publisher..No previous study has reported the role of SOCS2 in HSV-1 infection...Leong G, Moverare S, Brce J, Doyle N, Sjögren K, Dahlman Wright K, et al. Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro. Endocrinology. 2004;145:5525-31 pubmed..In summary, estrogen, via ERalpha, up-regulated hepatic expression of SOCS-2 and -3, probably through transcriptional activation. This indicates a novel mechanism of estrogen regulation of cytokine action. ..Horvat S, Medrano J. The high growth (hg) locus maps to a deletion in mouse chromosome 10. Genomics. 1996;36:546-9 pubmed..A dense map of markers around hg constructed here should allow identification of markers in homologous regions in domestic animals and humans, which may be utilized to assess the role of the hg locus in these other species. ..Babon J, Lucet I, Murphy J, Nicola N, Varghese L. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462:1-13 pubmed publisher..These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. ..Cargill S, Medrano J, Anderson G. Infertility in a line of mice with the high growth mutation is due to luteal insufficiency resulting from disruption at the hypothalamic-pituitary axis. Biol Reprod. 1999;61:283-7 pubmed..Luteal failure in HG females may be due to insufficient PRL as required for establishment and early maintenance of the CL during pregnancy in mice. ..Turnley A. Role of SOCS2 in growth hormone actions. Trends Endocrinol Metab. 2005;16:53-8 pubmed..Suppressor of cytokine signaling-2 (SOCS2) is one such intracellular regulator of GH signal transduction...Kazi J, Ronnstrand L. Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. Mol Oncol. 2013;7:693-703 pubmed publisherThe suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of E3 ubiquitin ligases. SOCS2 is known to regulate signal transduction by cytokine receptors and receptor tyrosine kinases...Farber C, Chitwood J, Lee S, Verdugo R, Islas Trejo A, Rincon G, et al. Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice. BMC Genet. 2008;9:34 pubmed publisher..The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V (Scg5; also referred to as Sgne1), as a candidate gene for growth traits...Knosp C, Schiering C, Spence S, Carroll H, Nel H, Osbourn M, et al. Regulation of Foxp3+ inducible regulatory T cell stability by SOCS2. J Immunol. 2013;190:3235-45 pubmed publisher..proteins are key regulators of CD4(+) T cell differentiation, and in particular, we have recently shown that SOCS2 inhibits the development of Th2 cells and allergic immune responses...McBerry C, Gonzalez R, Shryock N, Dias A, Aliberti J. SOCS2-induced proteasome-dependent TRAF6 degradation: a common anti-inflammatory pathway for control of innate immune responses. PLoS ONE. 2012;7:e38384 pubmed publisher..events essential for the development of immune responses--is targeted by both lipoxins and L-kynurenine via an AhR/SOCS2-dependent pathway...