The biology and mechanism of action of suppressor of cytokine signaling 3

References

• Anderson P, Sundstedt A, Li L, O'Neill EJ, Li SL, Wraith DC, Wang P. 2003. Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in T(h)1 and T(h)2 cells. Int Immunol. 15:1309–1317.
   PubMed Web of Science ®Google Scholar
• Babon JJ, Yao SG, DeSouza DP, Harrison CF, Fabri LJ, Liepinsh E, Scrofani SD, Baca M, Norton RS. 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.
   PubMed Web of Science ®Google Scholar
• Babon JJ, McManus EJ, Yao SG, DeSouza DP, Mielke LA, Sprigg NS, Willson TA, Hilton DJ, Nicola NA, Baca M, Nicholson SE, Norton RS. 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.
   PubMed Web of Science ®Google Scholar
• Babon JJ, Sabo JK, Soetopo A, Yao SG, Bailey MF, Zhang JG, Nicola NA, Norton RS. 2008. The SOCS box domain of SOCS3: Structure and interaction with the elonginBC-Cullin5 ubiquitin ligase. J Mol Biol. 381:928–940.
   PubMed Web of Science ®Google Scholar
• Babon JJ, Sabo JK, Zhang JG, Nicola NA, Norton RS. 2009. The SOCS box encodes a hierarchy of affinities for Cullin5: Implications for ubiquitin ligase formation and cytokine signalling suppression. J Mol Biol. 387:162–174.
   PubMed Web of Science ®Google Scholar
• Babon JJ, Kershaw NJ, Murphy JM, Varghese L, Laktyushin A, Lucet IS, Norton RS, Nicola NA. 2011. Suppression of cytokine signaling by SOCS3: Characterization of the mode of inhibition and the basis of its specificity. Immunity. 36:239–250.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Bergamin E, Wu J, Hubbard SR. 2006. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Structure. 14:1285–1292.
   PubMed Web of Science ®Google Scholar
• Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. 1998. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell. 1:619–625.
   PubMed Web of Science ®Google Scholar
• Bjorbaek C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG. 2000. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr(985). J Biol Chem. 275:40649–40657.
   PubMed Web of Science ®Google Scholar
• Boyle K, Egan P, Rakar S, Willson TA, Wicks IP, Metcalf D, Hilton DJ, Nicola NA, Alexander WS, Roberts AW, Robb L. 2007. The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivo. Blood. 110:1466–1474.
   PubMed Web of Science ®Google Scholar
• Boyle K, Zhang JG, Nicholson SE, Trounson E, Babon JJ, McManus EJ, Nicola NA, Robb L. 2009. 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. 21:394–404.
   PubMed Web of Science ®Google Scholar
• Brender C, Tannahill GM, Jenkins BJ, Fletcher J, Columbus R, Saris CJ, Ernst M, Nicola NA, Hilton DJ, Alexander WS, Starr R. 2007. Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27. Blood. 110:2528–2536.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Callus BA, Mathey-Prevot B. 2002. SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc. Oncogene. 21:4812–4821.
   PubMed Web of Science ®Google Scholar
• Cao W, Yang YQ, Wang ZY, Liu AL, Fang L, Wu FL, Hong J, Shi YF, Leung S, Dong C, Zhang JWZ. 2011. Leukemia inhibitory factor inhibits T helper 17 cell differentiation and confers treatment effects of neural progenitor cell therapy in autoimmune disease. Immunity. 35:273–284.
   PubMed Web of Science ®Google Scholar
• Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ. 2006. Selective regulatory function of SOCS3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA. 103:8137–8142.
   PubMed Web of Science ®Google Scholar
• Clahsen T, Lehmann U, Stross C, Hermanns HM, Volkmer-Engert R, Schneider-Mergener J, Heinrich PC, Schaper F. 2005. The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling. Cell Signal. 17:559–569.
   PubMed Web of Science ®Google Scholar
• Cohney SJ, Sanden D, Cacalano NA, Yoshimura A, Mui A, Migone TS, Johnston JA. 1999. SOCS-3 is tryrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol Cell Biol. 19:4980–4988.
   PubMed Web of Science ®Google Scholar
• Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, Greenhalgh CJ, Forster I, Clausen BE, Nicola NA, Metcalf D, Hilton DJ, Roberts AW, Alexander WS. 2003. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 4:540–545.
   PubMed Web of Science ®Google Scholar
• Croker BA, Metcalf D, Robb L, Wei W, Mifsud S, DiRago L, Cluse LA, Sutherland KD, Hartley L, Williams E, Zhang JG, Hilton DJ, Nicola NA, Alexander WS, Roberts AW. 2004. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity. 20:153–165.
   PubMed Web of Science ®Google Scholar
• Croker BA, Mielke LA, Wormald S, Metcalf D, Kiu H, Alexander WS, Hilton DJ, Roberts AW. 2008. SOCS3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiation. Exp Hematol. 36:786–798.
   PubMed Web of Science ®Google Scholar
• Croker BA, Kiu H, Pellegrini M, Toe J, Preston S, Metcalf D, O'Donnell JA, Cengia LH, McArthur K, Nicola NA, Alexander WS, Roberts AW. 2011. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3. Immunol Cell Biol.. 90 1: 124–129.
   PubMed Web of Science ®Google Scholar
• Cui Q, Jiang W, Wang YX, Lv C, Luo JJ, Zhang W, Lin F, Yin YX, Cai R, Wei P, Qian C. 2008. Transfer of suppressor of cytokine signaling 3 by an oncolytic adenovirus induces potential antitumor activities in hepatocellular carcinoma. Hepatology. 47:105–112.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Egwuagu CE, Yu CR, Zhang MF, Mahdi RM, Kim SJ, Gery I. 2002. Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: Implications for Th cell lineage commitment and maintenance. J Immunol. 168:3181–3187.
   PubMed Web of Science ®Google Scholar
• Emery B, Cate HS, Marriottt M, Merson T, Binder MD, Snell C, Soo PY, Murray S, Croker B, Zhang JG, Alexander WS, Cooper H, Butzkueven H, Kilpatrick TJ. Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. Proc Natl Acad Sci USA. 2006a; 103:7859–7864.
   PubMed Web of Science ®Google Scholar
• Emery B, Merson TD, Snell C, Young KM, Ernst M, Kilpatrick TJ. SOCS3 negatively regulates LIF signaling in neural precursor cells. Mol Cell Neurosci. 2006b; 31:739–747.
   PubMed Web of Science ®Google Scholar
• Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A. 1997. A new protein containing an SH2 domain that inhibits JAK kinases. Nature. 387:921–924.
   PubMed Web of Science ®Google Scholar
• Ernst M, Najdovska M, Grail D, Lundgren-May T, Buchert M, Tye H, Matthews VB, Armes J, Bhathal PS, Hughes NR, Marcusson EG, Karras JG, Na SQ, Sedgwick JD, Hertzog PJ, Jenkins BJ. 2008. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest. 118:1727–1738.
   PubMed Web of Science ®Google Scholar
• Fairlie WD, De Souza D, Nicola NA, Baca M. 2003. Negative regulation of gp130 signalling mediated through tyrosine-757 is not dependent on the recruitment of SHP2. Biochem J. 372:495–502.
   PubMed Web of Science ®Google Scholar
• Forrai A, Boyle K, Hart AH, Hartley L, Rakar S, Willson TA, Simpson KM, Roberts AW, Alexander WS, Voss AK, Robb L. 2006. Absence of suppressor of cytokine signalling 3 reduces self-renewal and promotes differentiation in murine embryonic stem cells. Stem Cells. 24:604–614.
   PubMed Web of Science ®Google Scholar
• Greenhalgh CJ, Metcalf D, Thaus AL, Corbin JE, Uren R, Morgan PO, Fabri LJ, Zhang JG, Martin HM, Willson TA, Billestrup N, Nicola NA, Baca M, Alexander WS, Hilton DJ. 2002. Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling. J Biol Chem. 277:40181–40184.
   PubMed Web of Science ®Google Scholar
• Grucza RA, Bradshaw JM, Futterer K, Waksman G. 1999. SH2 domains: From structure to energetics, a dual approach to the study of structure-function relationships. Med Res Rev. 19:273–293.
   PubMed Web of Science ®Google Scholar
• Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D, Nicola NA. 1998. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci USA. 95:114–119.
   PubMed Web of Science ®Google Scholar
• Hortner M, Nielsch U, Mayr LM, Heinrich PC, Haan S. A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. Eur J Biochem. 2002a; 269:2516–2526.
   PubMedGoogle Scholar
• Hortner M, Nielsch U, Mayr LM, Johnston JA, Heinrich PC, Haan S. Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction. J Immunol. 2002b; 169:1219–1227.
   PubMed Web of Science ®Google Scholar
• Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C, Flier JS. 2004. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of SOCS3. Nat Med. 10:734–738.
   PubMed Web of Science ®Google Scholar
• Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Thierfelder WE, Kreider B, Silvennoinen O. 1994. Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci. 19:222–227.
   PubMed Web of Science ®Google Scholar
• Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI. 2004. VHL-box and SOCS-box domains determine binding specificity for Cul2–Rbx1 and Cul5–Rbx2 modules of ubiquitin ligases. Genes Dev. 18:3055–3065.
   PubMed Web of Science ®Google Scholar
• Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. 2005. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 280:7038–7048.
   PubMed Web of Science ®Google Scholar
• Kievit P, Howard JK, Badman MK, Balthasar N, Coppari R, Mori H, Lee CE, Elmquist JK, Yoshimura A, Flier JS. 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.
   PubMed Web of Science ®Google Scholar
• Kimura A, Kinjyo I, Matsumura Y, Mori H, Mashima R, Harada M, Chien KR, Yasukawa H, Yoshimura A. 2004. SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte colony-stimulating factor receptor signaling. J Biol Chem. 279:6905–6910.
   PubMed Web of Science ®Google Scholar
• Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H, Himeno K, Takaesu G, Kobayashi T, Yoshimura A. 2006. Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J Exp Med. 203:1021–1031.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF, Rossjohn J. 2006. The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood. 107:176–183.
   PubMed Web of Science ®Google Scholar
• Mahrour N, Redwine WB, Florens L, Swanson SK, Martin-Brown S, Bradford WD, Staehling-Hampton K, Washburn MP, Conaway RC, Conaway JW. 2008. Characterization of Cullin-box sequences that direct recruitment of Cul2–Rbx1 and Cul5–Rbx2 modules to elongin BC-based ubiquitin ligases. J Biol Chem. 283:8005–8013.
   PubMed Web of Science ®Google Scholar
• Matsumoto A, Seki Y, Watanabe R, Hayashi K, Johnston JA, Harada Y, Abe R, Yoshimura A, Kubo M. 2003. A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. J Exp Med. 197:425–436.
   PubMed Web of Science ®Google Scholar
• Matsumura Y, Kobayashi T, Ichiyama K, Yoshida R, Hashimoto M, Takimoto T, Tanaka K, Chinen T, Shichita T, Wyss-Coray T, Sato K, Yoshimura A. 2007. Selective expansion of Foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J Immunol. 179:2170–2179.
   PubMed Web of Science ®Google Scholar
• Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A. 2004. SOCS3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med. 10:739–743.
   PubMed Web of Science ®Google Scholar
• Naka T, Narazaki M, Hirata M, Matsumoto T, Minamoto S, Aono A, Nishimoto N, Kajita T, Taga T, Yoshizaki K, Akira S, Kishimoto T. 1997. Structure and function of a new STAT-induced STAT inhibitor. Nature. 387:924–929.
   PubMed Web of Science ®Google Scholar
• Nicholson SE, De Souza D, Fabri LJ, Corbin J, Willson TA, Zhang JG, Silva A, Asimakis M, Farley A, Nash AD, Metcalf D, Hilton DJ, Nicola NA, Baca M. 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.
   PubMed Web of Science ®Google Scholar
• Nicholson SE, Metcalf D, Sprigg NS, Columbus R, Walker F, Silva A, Cary D, Willson TA, Zhang JG, Hilton DJ, Alexander WS, Nicola NA. 2005. Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling. Proc Natl Acad Sci USA. 102:2328–2333.
   PubMed Web of Science ®Google Scholar
• Niwa Y, Kanda H, Shikauchi Y, Saiura A, Matsubara K, Kitagawa T, Yamamoto J, Kubo T, Yoshikawa H. 2005. Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene. 24:6406–6417.
   PubMed Web of Science ®Google Scholar
• Ogata H, Chinen T, Yoshida T, Kinjyo I, Takaesu G, Shiraishi H, Iida M, Kobayashi T, Yoshimura A. Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta 1 production. Oncogene. 2006a; 25:2520–2530.
   PubMed Web of Science ®Google Scholar
• Ogata H, Kobayashi T, Chinen T, Takaki H, Sanada T, Minoda Y, Koga K, Takaesu G, Maehara Y, Iida M, Yoshimura A. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology. 2006b; 131:179–193.
   PubMed Web of Science ®Google Scholar
• Ohh M, Takagi Y, Aso T, Stebbins CE, Pavletich NP, Zbar B, Conaway RC, Conaway JW, Kaelin WGJr. 1999. Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel–Lindau protein. J Clin Invest. 104:1583–1591.
   PubMed Web of Science ®Google Scholar
• Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG. 2000. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel–Lindau protein. Nat Cell Biol. 2:423–427.
   PubMed Web of Science ®Google Scholar
• Pazienza V, Clement S, Pugnale P, Conzelman S, Foti M, Mangia A, Negro F. 2007. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology. 45:1164–1171.
   PubMed Web of Science ®Google Scholar
• Pellegrini M, Calzascia T, Toe JG, Preston SP, Lin AE, Elford AR, Shahinian A, Lang PA, Lang KS, Morre M, Assouline B, Lahl K, Sparwasser T, Tedder TF, Paik JH, DePinho RA, Basta S, Ohashi PS, Mak TW. 2011. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell. 144:601–613.
   PubMed Web of Science ®Google Scholar
• Pillemer BBL, Xu H, Oriss TB, Qi ZB, Ray A. 2007. Deficient SOCS3 expression in CD4(+)CD25(+)FoxP3(+) regulatory T cells and SOCS3-mediated suppression of Treg function. Eur J Immunol. 37:2082–2089.
   PubMed Web of Science ®Google Scholar
• Qin HW, Wang LF, Feng T, Elson CO, Niyongere SA, Lee SJ, Reynolds SL, Weaver CT, Roarty K, Serra R, Benveniste EN, Cong YZ. 2009. TGF-beta promotes Th17 cell development through inhibition of SOCS3. J Immunol. 183:97–105.
   PubMed Web of Science ®Google Scholar
• Ram PA, Waxman DJ. 1999. SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms. J Biol Chem. 274:35553–35561.
   PubMed Web of Science ®Google Scholar
• Ram PA, Waxman DJ. 2000. Role of the cytokine-inducible SH2 protein CIS in desensitization of STAT5b signaling by continuous growth hormone. J Biol Chem. 275:39487–39496.
   PubMed Web of Science ®Google Scholar
• Riehle KJ, Campbell JS, McMahan RS, Johnson MM, Beyer RP, Bammler TK, Fausto N. 2008. Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3. J Exp Med. 205:91–103.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, Hilton DJ, Alexander WS. 2001. Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc Natl Acad Sci USA. 98:9324–9329.
   PubMed Web of Science ®Google Scholar
• Rogers S, Wells R, Rechsteiner M. 1986. Amino acid sequences common to rapidly degraded proteins: The PEST hypothesis. Science. 234:364–368.
   PubMed Web of Science ®Google Scholar
• Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A. 1999. Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain. Genes Cells. 4:339–351.
   PubMed Web of Science ®Google Scholar
• Schmitz J, Weissenbach M, Haan S, Heinrich PC, Schaper F. 2000. SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130. J Biol Chem. 275:12848–12856.
   PubMed Web of Science ®Google Scholar
• Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, Komine O, Hamano S, Himeno K, Inagaki-Ohara K, Cacalano N, O'Garra A, Oshida T, Saito H, Johnston JA, Yoshimura A, Kubo M. 2003. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 9:1047–1054.
   PubMed Web of Science ®Google Scholar
• Shouda T, Yoshida T, Hanada T, Wakioka T, Oishi M, Miyoshi K, Komiya S, Kosai K, Hanakawa Y, Hashimoto K, Nagata K, Yoshimura A. 2001. Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J Clin Invest. 108:1781–1788.
   PubMed Web of Science ®Google Scholar
• Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, Martinez-Carrasco I, Connolly L, He G. 2009. SOCS3 Deletion promotes optic nerve regeneration in vivo. Neuron. 64:617–623.
   PubMed Web of Science ®Google Scholar
• Song MM, Shuai K. 1998. The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem. 273:35056–35062.
   PubMed Web of Science ®Google Scholar
• Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ. 1997. A family of cytokine-inducible inhibitors of signalling. Nature. 387:917–921.
   PubMed Web of Science ®Google Scholar
• Stross C, Radtke S, Clahsen T, Gerlach C, Volkmer-Engert R, Schaper F, Heinrich PC, Hermanns HM. 2006. Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem. 281:8458–8468.
   PubMed Web of Science ®Google Scholar
• Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, He Z. 2011. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 480 7377: 372–375.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Takahashi Y, Dominici M, Swift J, Nagy C, Ihle JN. 2006. Trophoblast stem cells rescue placental defect in SOCS3-deficient mice. J Biol Chem. 281:11444–11445.
   PubMed Web of Science ®Google Scholar
• Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, Esposito B, Perez N, Yasukawa H, Van Snick J, Yoshimura A, Tedgui A, Mallat Z. 2009. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med. 206:2067–2077.
   PubMed Web of Science ®Google Scholar
• Verdier F, Chretien S, Muller O, Varlet P, Yoshimura A, Gisselbrecht S, Lacombe C, Mayeux P. 1998. Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated Cis protein. J Biol Chem. 273:28185–28190.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Wilks AF, Oates AC. 1996. The JAK/STAT pathway. Cancer Surv. 27:139–163.
   PubMedGoogle Scholar
• Wisniewski JA, Borish L. 2011. Novel cytokines and cytokine-producing T cells in allergic disorders. Allergy Asthma Proc. 32:83–94.
   PubMed Web of Science ®Google Scholar
• Wong PKK, Egan PJ, Croker BA, O'Donnell K, Sims NA, Drake S, Kiu H, McManus EJ, Alexander WS, Roberts AW, Wicks IP. 2006. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest. 116:1571–1581.
   PubMed Web of Science ®Google Scholar
• Wormald S, Zhang JG, Krebes DL, Mielke LA, Silver J, Alexander WS, Speed TP, Nicola NA, Hilton DJ. 2006. The comparative roles of suppressor of cytokine signaling-1 and-3 in the inhibition and desensitization of cytokine signaling. J Biol Chem. 281:11135–11143.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Yamaguchi M, Miyasaka N, Miura O. 2003. SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta 2 subunit. Biochem Biophys Res Commun. 310:1188–1193.
   PubMed Web of Science ®Google Scholar
• Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A. 1999. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J. 18:1309–1320.
   PubMed Web of Science ®Google Scholar
• Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, Harris CC, Herman JG. 2001. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet. 28:29–35.
   PubMed Web of Science ®Google Scholar
• Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T, Aki D, Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR, Yoshimura A. 2003. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol. 4:551–556.
   PubMed Web of Science ®Google Scholar
• Zhang JG, Metcalf D, Rakar S, Asimakis M, Greenhalgh CJ, Willson TA, Starr R, Nicholson SE, Carter W, Alexander WS, Hilton DJ, Nicola NA. 2001. The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo. Proc Natl Acad Sci USA. 98:13261–13265.
   PubMed Web of Science ®Google Scholar
• Zhang R, Dhillon H, Yin H, Yoshimura A, Lowell BB, Maratos-Flier E, Flier JS. 2008. Selective inactivation of SOCS3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology. 149:5654–5661.
   PubMed Web of Science ®Google Scholar
• Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. 2002. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 416:703–709.
   PubMed Web of Science ®Google Scholar