628
Views
29
CrossRef citations to date
0
Altmetric
Review Article

Understanding SOCS protein specificity

, &
Pages 104-117 | Received 19 Jun 2018, Accepted 28 Aug 2018, Published online: 15 Oct 2018

References

  • Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, et al. 1999. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98:597–608.
  • Aman MJ, Migone TS, Sasaki A, Ascherman DP, Zhu MH, Soldaini E, Imada K, et al. 1999. CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling. J Biol Chem 274:30266–30272.
  • Babon JJ, Kershaw NJ, Murphy JM, Varghese LN, Laktyushin A, Young SN, Lucet IS, et al. 2012. Suppression of cytokine signaling by SOCS3: Characterization of the mode of inhibition and the basis of its specificity. Immunity 36:239–250.
  • Babon JJ, McManus EJ, Yao S, DeSouza DP, Mielke LA, Sprigg NS, Willson TA, et al. 2006. The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability. Mol Cell 22:205–216.
  • Babon JJ, Nicola NA. 2012. The biology and mechanism of action of suppressor of cytokine signaling 3. Growth Factors 30:207–219.
  • Babon JJ, Varghese LN, Nicola NA. 2014. Inhibition of IL-6 family cytokines by SOCS3. Semin Immunol 26:13–19.
  • Babon JJ, Yao S, DeSouza DP, Harrison CF, Fabri LJ, Liepinsh E, Scrofani SD, et al. 2005. Secondary structure assignment of mouse SOCS3 by NMR defines the domain boundaries and identifies an unstructured insertion in the SH2 domain. FEBS J 272:6120–6130.
  • Banks AS, Li J, McKeag L, Hribal ML, Kashiwada M, Accili D, Rothman PB. 2005. Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans. J Clin Invest 115:2462–2471.
  • Bergamin E, Wu J, Hubbard SR. 2006. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Structure 14:1285–1292.
  • Brender C, Columbus R, Metcalf D, Handman E, Starr R, Huntington N, Tarlinton D, et al. 2004. SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function. Mol Cell Biol 24:6094–6103.
  • Bullock AN, Debreczeni JE, Edwards AM, Sundstrom M, Knapp S. 2006. Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Proc Natl Acad Sci USA 103:7637–7642.
  • Bullock AN, Rodriguez MC, Debreczeni JE, Songyang Z, Knapp S. 2007. Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. Structure 15:1493–1504.
  • Chandrashekaran IR, Mohanty B, Linossi EM, Dagley LF, Leung EW, Murphy JM, Babon JJ, et al. 2015. Structure and functional characterization of the conserved JAK interaction region in the intrinsically disordered N-terminus of SOCS5. Biochemistry 54: 4672–4682.
  • Choi YB, Son M, Park M, Shin J, Yun Y. 2010. SOCS-6 negatively regulates T cell activation through targeting p56lck to proteasomal degradation. J Biol Chem 285:7271–7280.
  • Chong MM, Cornish AL, Darwiche R, Stanley EG, Purton JF, Godfrey DI, Hilton DJ, et al. 2003. Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation. Immunity 18:475–487.
  • Cornish AL, Chong MM, Davey GM, Darwiche R, Nicola NA, Hilton DJ, Kay TW, et al. 2003. Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cells. J Biol Chem 278:22755–22761.
  • Cornish AL, Davey GM, Metcalf D, Purton JF, Corbin JE, Greenhalgh CJ, Darwiche R, et al. 2003. Suppressor of cytokine signaling-1 has IFN-gamma-independent actions in T cell homeostasis. J Immunol 170:878–886.
  • Croker BA, Kiu H, Nicholson SE. 2008. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 19:414–422.
  • Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, et al. 2003. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol 4:540–545.
  • Croker BA, Metcalf D, Robb L, Wei W, Mifsud S, DiRago L, Cluse LA, et al. 2004. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 20:153–165.
  • Croom HA, Izon DJ, Chong MM, Curtis DJ, Roberts AW, Kay TW, Hilton DJ, et al. 2008. Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3. Mol Immunol 45:2888–2896.
  • Davey GM, Starr R, Cornish AL, Burghardt JT, Alexander WS, Carbone FR, Surh CD, Heath WR. 2005. SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential. J Exp Med 202:1099–1108.
  • De Souza D, Fabri LJ, Nash A, Hilton DJ, Nicola NA, Baca M. 2002. SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry 41:9229–9236.
  • Delconte RB, Kolesnik TB, Dagley LF, Rautela J, Shi W, Putz EM, Stannard K, et al. 2016. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 17:816–824.
  • Delgoffe GM, Murray PJ, Vignali DA. 2011. Interpreting mixed signals: The cell's cytokine conundrum. Curr Opin Immunol 23:632–638.
  • Ernst M, Jenkins BJ. 2004. Acquiring signalling specificity from the cytokine receptor gp130. Trends Genet 20:23–32.
  • Eyles JL, Metcalf D, Grusby MJ, Hilton DJ, Starr R. 2002. Negative regulation of interleukin-12 signaling by suppressor of cytokine signaling-1. J Biol Chem 277:43735–43740.
  • Feng ZP, Chandrashekaran IR, Low A, Speed TP, Nicholson SE, Norton RS. 2012. The N-terminal domains of SOCS proteins: A conserved region in the disordered N-termini of SOCS4 and 5. Proteins 80:946–957.
  • Fenner JE, Starr R, Cornish AL, Zhang JG, Metcalf D, Schreiber RD, Sheehan K, Hilton DJ, Alexander WS, Hertzog PJ. 2006. Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity. Nat Immunol 7:33–39.
  • Forrai A, Boyle K, Hart AH, Hartley L, Rakar S, Willson TA, Simpson KM, et al. 2006. Absence of suppressor of cytokine signalling 3 reduces self-renewal and promotes differentiation in murine embryonic stem cells. Stem Cells 24:604–614.
  • Fujimoto M, Tsutsui H, Yumikura-Futatsugi S, Ueda H, Xingshou O, Abe T, Kawase I, Nakanishi K, Kishimoto T, Naka T. 2002. A regulatory role for suppressor of cytokine signaling-1 in T(h) polarization in vivo. Int Immunol 14:1343–1350.
  • Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, Davey HW, et al. 2002. 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 16:1394–1406.
  • Greenhalgh CJ, Metcalf D, Thaus AL, Corbin JE, Uren R, Morgan PO, Fabri LJ, et al. 2002. Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling. J Biol Chem 277:40181–40184.
  • Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, et al. 1998. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci USA 95:114–119.
  • Howard JK, Flier JS. 2006. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab 17:365–371.
  • Huang H, Li L, Wu C, Schibli D, Colwill K, Ma S, Li C, et al. 2008. Defining the specificity space of the human SRC homology 2 domain. Mol Cell Proteomics 7:768–784.
  • Hunter T. 2014. The genesis of tyrosine phosphorylation. Cold Spring Harb Perspect Biol 6:a020644.
  • Kamura T, Sato S, Haque D, Liu L, Kaelin WG, Jr., Conaway RC, Conaway JW. 1998. The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Genes Dev 12:3872–3881.
  • Kaneko T, Huang H, Zhao B, Li L, Liu H, Voss CK, Wu C, et al. 2010. Loops govern SH2 domain specificity by controlling access to binding pockets. Sci Signal 3:ra34.
  • Kedzierski L, Clemens EB, Bird NL, Kile BT, Belz GT, Nicola NA, Kedzierska K, Nicholson SE. 2015. SOCS4 is dispensable for an efficient recall response to influenza despite being required for primary immunity. Immunol Cell Biol 93:909–913.
  • Kedzierski L, Linossi EM, Kolesnik TB, Day EB, Bird NL, Kile BT, Belz GT, et al. 2014. Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection. PLoS Pathog 10:e1004134.
  • Kedzierski L, Tate MD, Hsu AC, Kolesnik TB, Linossi EM, Dagley L, Dong Z, et al. 2017. Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling. Elife 6. doi:10.7554/eLife.20444.
  • Kershaw NJ, Murphy JM, Liau NP, Varghese LN, Laktyushin A, Whitlock EL, Lucet IS, et al. 2013. SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. Nat Struct Mol Biol 20:469–476.
  • Kievit P, Howard JK, Badman MK, Balthasar N, Coppari R, Mori H, Lee CE, et al. 2006. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab 4:123–132.
  • Kiu H, Nicholson SE. 2012. Biology and significance of the JAK/STAT signalling pathways. Growth Factors 30:88–106.
  • Krebs DL, Metcalf D, Merson TD, Voss AK, Thomas T, Zhang JG, Rakar S, et al. 2004. Development of hydrocephalus in mice lacking SOCS7. Proc Natl Acad Sci USA 101:15446–15451.
  • Krebs DL, Uren RT, Metcalf D, Rakar S, Zhang JG, Starr R, De Souza DP, et al. 2002. SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Mol Cell Biol 22:4567–4578.
  • Ladbury JE, Lemmon MA, Zhou M, Green J, Botfield MC, Schlessinger J. 1995. Measurement of the binding of tyrosyl phosphopeptides to SH2 domains: A reappraisal. Proc Natl Acad Sci USA 92:3199–3203.
  • Lang R, Pauleau AL, Parganas E, Takahashi Y, Mages J, Ihle JN, Rutschman R, Murray PJ. 2003. SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol 4:546–550.
  • Lawrenson ID, Krebs DL, Linossi EM, Zhang JG, McLennan TJ, Collin C, McRae HM, et al. 2017. Cortical layer inversion and deregulation of reelin signaling in the absence of SOCS6 and SOCS7. Cereb Cortex 27:576–588.
  • Li L, Gronning LM, Anderson PO, Li S, Edvardsen K, Johnston J, Kioussis D, et al. 2004. Insulin induces SOCS-6 expression and its binding to the p85 monomer of phosphoinositide 3-kinase, resulting in improvement in glucose metabolism. J Biol Chem 279:34107–34114.
  • Li S, Chen S, Xu X, Sundstedt A, Paulsson KM, Anderson P, Karlsson S, et al. 2000. Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells. J Exp Med 191:985–994.
  • Liau NPD, Babon JJ. 2018. Expression and purification of JAK1 and SOCS1 for structural and biochemical studies. Methods Mol Biol 1725:267–280.
  • Liau NPD, Laktyushin A, Lucet IS, Murphy JM, Yao S, Whitlock E, Callaghan K, et al. 2018. The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun 9:1558.
  • Lin JX, Leonard WJ. 2017. The common cytokine receptor gamma chain family of cytokines. Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a028449.
  • Linossi EM, Chandrashekaran IR, Kolesnik TB, Murphy JM, Webb AI, Willson TA, Kedzierski L, et al. 2013. Suppressor of Cytokine Signaling (SOCS) 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1. PLoS One 8:e70536.
  • Linossi EM, Nicholson SE. 2012. The SOCS box-adapting proteins for ubiquitination and proteasomal degradation. IUBMB Life 64:316–323.
  • Liu BA, Engelmann BW, Nash PD. 2012. The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction. FEBS Lett 586:2597–2605.
  • Liu BA, Jablonowski K, Raina M, Arce M, Pawson T, Nash PD. 2006. The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling. Mol Cell 22:851–868.
  • Liu BA, Jablonowski K, Shah EE, Engelmann BW, Jones RB, Nash PD. 2010. SH2 domains recognize contextual peptide sequence information to determine selectivity. Mol Cell Proteomics 9:2391–2404.
  • Liu L, Brown D, McKee M, Lebrasseur NK, Yang D, Albrecht KH, Ravid K, Pilch PF. 2008. Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell Metab 8:310–317.
  • Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, et al. 1999. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell 98:617–627.
  • Matsumoto A, Seki Y, Kubo M, Ohtsuka S, Suzuki A, Hayashi I, Tsuji K, et al. 1999. Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. Mol Cell Biol 19:6396–6407.
  • Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS. 2000. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 405:1069–1073.
  • Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, et al. 2004. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10:739–743.
  • Murray PJ. 2007. The JAK-STAT signaling pathway: Input and output integration. J Immunol 178:2623–2629.
  • Naka T, Tsutsui H, Fujimoto M, Kawazoe Y, Kohzaki H, Morita Y, Nakagawa R, et al. 2001. SOCS-1/SSI-1-deficient NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-gamma and IL-4 signaling in vivo. Immunity 14:535–545.
  • Narazaki M, Fujimoto M, Matsumoto T, Morita Y, Saito H, Kajita T, Yoshizaki K, et al. 1998. Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling. Proc Natl Acad Sci USA 95:13130–13134.
  • Nicholson SE, De Souza D, Fabri LJ, Corbin J, Willson TA, Zhang JG, Silva A, et al. 2000. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130. Proc Natl Acad Sci USA 97:6493–6498.
  • Nicholson SE, Willson TA, Farley A, Starr R, Zhang JG, Baca M, Alexander WS, et al. 1999. 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 18:375–385.
  • O'Shea JJ, Murray PJ. 2008. Cytokine signaling modules in inflammatory responses. Immunity 28:477–487.
  • Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, et al. 2015. Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance. J Exp Med 212:2095–2113.
  • Palmer DC, Restifo NP. 2009. Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol 30:592–602.
  • Piganis RA, De Weerd NA, Gould JA, Schindler CW, Mansell A, Nicholson SE, Hertzog PJ. 2011. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon alpha receptor (IFNAR1)-associated tyrosine kinase Tyk2. J Biol Chem 286:33811–33818.
  • Putz EM, Guillerey C, Kos K, Stannard K, Miles K, Delconte RB, Takeda K, et al. 2017. Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis. Oncoimmunology 6:e1267892.
  • Qing Y, Costa-Pereira AP, Watling D, Stark GR. 2005. Role of tyrosine 441 of interferon-gamma receptor subunit 1 in SOCS-1-mediated attenuation of STAT1 activation. J Biol Chem 280:1849–1853.
  • Ramanathan S, Gagnon J, Leblanc C, Rottapel R, Ilangumaran S. 2006. Suppressor of cytokine signaling 1 stringently regulates distinct functions of IL-7 and IL-15 in vivo during T lymphocyte development and homeostasis. J Immunol 176:4029–4041.
  • Robb L, Boyle K, Rakar S, Hartley L, Lochland J, Roberts AW, Alexander WS, Metcalf D. 2005. Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease. Proc Natl Acad Sci USA 102:16333–16338.
  • Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, et al. 2001. Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc Natl Acad Sci USA 98:9324–9329.
  • Rogers S, Wells R, Rechsteiner M. 1986. Amino acid sequences common to rapidly degraded proteins: The PEST hypothesis. Science 234:364–368.
  • Sadowski I, Stone JC, Pawson T. 1986. A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. Mol Cell Biol 6:4396–4408.
  • Sands WA, Woolson HD, Milne GR, Rutherford C, Palmer TM. 2006. Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol Cell Biol 26:6333–6346.
  • Simo S, Cooper JA. 2013. Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors. Dev Cell 27:399–411.
  • Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, Martinez-Carrasco I, Z et al. 2009. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64:617–623.
  • Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, et al. 1993. SH2 domains recognize specific phosphopeptide sequences. Cell 72:767–778.
  • Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, Barbacid M, et al. 1994. Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol 14:2777–2785.
  • Starr R, Fuchsberger M, Lau LS, Uldrich AP, Goradia A, Willson TA, Verhagen AM, et al. 2009. SOCS-1 binding to tyrosine 441 of IFN-gamma receptor subunit 1 contributes to the attenuation of IFN-gamma signaling in vivo. Immunol 183:4537–4544.
  • Starr R, Metcalf D, Elefanty AG, Brysha M, Willson TA, Nicola NA, Hilton DJ, Alexander WS. 1998. Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc Natl Acad Sci USA 95:14395–14399.
  • Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, et al. 1997. A family of cytokine-inducible inhibitors of signalling. Nature 387:917–921.
  • Takahashi Y, Carpino N, Cross JC, Torres M, Parganas E, Ihle JN. 2003. SOCS3: An essential regulator of LIF receptor signaling in trophoblast giant cell differentiation. EMBO J 22:372–384.
  • Tebbutt NC, Giraud AS, Inglese M, Jenkins B, Waring P, Clay FJ, Malki S, et al. 2002. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 8:1089–1097.
  • Ushiki T, Huntington ND, Glaser SP, Kiu H, Georgiou A, Zhang JG, Metcalf D, et al. 2016. Rapid Inflammation in Mice Lacking Both SOCS1 and SOCS3 in Hematopoietic Cells. PLoS One 11:e0162111.
  • Waksman G, Kominos D, Robertson SC, Pant N, Baltimore D, Birge RB, Cowburn D, et al. 1992. Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature 358:646–653.
  • Waksman G, Shoelson SE, Pant N, Cowburn D, Kuriyan J. 1993. Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: Crystal structures of the complexed and peptide-free forms. Cell 72:779–790.
  • Williams JJL, Alotaiq N, Mullen W, Burchmore R, Liu L, Baillie GS, Schaper F, et al. 2018. Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nat Commun 9:168.
  • Yang XO, Zhang H, Kim BS, Niu X, Peng J, Chen Y, Kerketta R, et al. 2013. The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation. Nat Immunol 14:732–740.
  • Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, et al. 1999. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J 18:1309–1320.
  • Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T, Aki D, Hanada T, et al. 2003. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol 4:551–556.
  • Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A. 1995. A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. EMBO J 14:2816–2826.
  • Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H. 2012. SOCS, inflammation, and autoimmunity. Front Immunol 3:20.
  • Zadjali F, Pike AC, Vesterlund M, Sun J, Wu C, Li SS, Ronnstrand L, et al. 2011. Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. J Biol Chem 286:480–490.
  • Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, et al. 1999. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci USA 96:2071–2076.
  • Zhang WN, Wang L, Wang Q, Luo X, Fang DF, Chen Y, Pan X, et al. 2012. CUEDC2 (CUE domain-containing 2) and SOCS3 (suppressors of cytokine signaling 3) cooperate to negatively regulate Janus kinase 1/signal transducers and activators of transcription 3 signaling. J Biol Chem 287:382–392.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.