IL-6 signal transduction and its physiological roles: the signal orchestration model (original) (raw)

References

• Abe K, Hirai M, Mizuno K, Higashi N, Sekimoto T, Miki T, Hirano T, Nakajima K (2001) The YXXQ motif in gp 130 is crucial for STAT3 phosphorylation at Ser727 through an H7-sensitive kinase pathway. Oncogene 20:3464–3474
  Article PubMed CAS Google Scholar
• Alexander WS, Rakar S, Robb L, Farley A, Willson TA, Zhang JG, Hartley L, Kikuchi Y, Kojima T, Nomura H, Hasegawa M, Maeda M, Fabri L, Jachno K, Nash A, Metcalf D, Nicola NA, Hilton DJ (1999) Suckling defect in mice lacking the soluble haemopoietin receptor NR6. Curr Biol 9:605–608
  Article PubMed CAS Google Scholar
• Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, De Benedetti F, Poli V, Ciliberto G (1998) Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 187:461–468
  Article PubMed CAS Google Scholar
• Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F (2000) Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation. J Immunol 165:2535–2543
  PubMed CAS Google Scholar
• Astaldi GC, Janssen MC, Lansdorp P, Willems C, Zeijlemaker WP, Oosterhof F (1980) Human endothelial culture supernatant (HECS): a growth factor for hybridomas. J Immunol 125:1411–1414
  PubMed CAS Google Scholar
• Atreya R, Mudter J, Finotto S, Mullberg J, Jostock T, Wirtz S, Schutz M, Bartsch B, Holtmann M, Becker C, Strand D, Czaja J, Schlaak JF, Lehr HA, Autschbach F, Schurmann G, Nishimoto N, Yoshizaki K, Ito H, Kishimoto T, Galle PR, Rose-John S, Neurath MF (2000) Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn’s disease and experimental colitis in vivo. Nat Med 6:583–588
  Article PubMed CAS Google Scholar
• Atsumi T, Ishihara K, Kamimura D, Ikushima H, Ohtani T, Hirota S, Kobayashi H, Park SJ, Saeki Y, Kitamura Y, Hirano T (2002) A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis. J Exp Med 196:979–990
  Article PubMed CAS Google Scholar
• Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11: 372–377
  Article PubMed CAS Google Scholar
• Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15:74–80
  Article PubMed CAS Google Scholar
• Bennett AM, Hausdorff SF, O’Reilly AM, Freeman RM, Neel BG (1996) Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression. Mol Cell Biol 16:1189–1202
  PubMed CAS Google Scholar
• Bernad A, Kopf M, Kulbacki R, Weich N, Koehler G, Gutierrez-Ramos JC (1994) Interleukin-6 is required in vivo for the regulation of stem cells and committed progenitors of the hematopoietic system. Immunity 1:725–731
  Article PubMed CAS Google Scholar
• Bethin KE, Vogt SK, Muglia LJ (2000) Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation. Proc Natl Acad Sci USA 97:9317–9322
  Article PubMed CAS Google Scholar
• Betz UA, Bloch W, van den Broek M, Yoshida K, Taga T, Kishimoto T, Addicks K, Rajewsky K, Muller W (1998) Postnatally-induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med 188:1955–1965
  Article PubMed CAS Google Scholar
• Borsellino N, Bonavida B, Ciliberto G, Toniatti C, Travali S, D’Alessandro N (1999) Blocking signaling through the Gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity. Cancer 85:134–144
  Article PubMed CAS Google Scholar
• Bowcock AM, Kidd JR, Lathrop GM, Daneshvar L, May LT, Ray A, Sehgal PB, Kidd KK, Cavalli-Sforza LL (1988) The human “interferon-β2/hepatocyte stimulating factor/interleukin-6” gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8–16
  Article PubMed CAS Google Scholar
• Bravo J, Heath JK (2000) Receptor recognition by gp130 cytokines. EMBO J 19:2399–2411
  Article PubMed CAS Google Scholar
• Bromberg J, Darnell JE, Jr. (2000) The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19:2468–2473
  Article PubMed CAS Google Scholar
• Brown S, Hu N, Hombria JC (2001) Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless. Curr Biol 11:1700–1705
  Article PubMed CAS Google Scholar
• Brunello AG, Weissenberger J, Kappeler A, Vallan C, Peters M, Rose-John S, Weis J (2000) Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor αdouble-transgenic mice. Am J Pathol 157:1485–1493
  PubMed CAS Google Scholar
• Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, Emery B, Turnley AM, Petratos S, Ernst M, Bartlett PF, Kilpatrick TJ (2002) LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nat Med 8:613–619
  Article PubMed CAS Google Scholar
• Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L (1993) Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 90:10061–10065
  Article PubMed CAS Google Scholar
• Chen HW, Chen X, Oh SW, Marinissen MJ, Gutkind JS, Hou SX (2002) mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. Genes Dev 16:388–398
  Article PubMed CAS Google Scholar
• Chesnokova V, Auernhammer CJ, Melmed S (1998) Murine leukemia inhibitory factor gene disruption attenuates the hypothalamo-pituitary-adrenal axis stress response. Endocrinology 139:2209–2216
  Article PubMed CAS Google Scholar
• Chomarat P, Banchereau J, Davoust J, Palucka AK (2000) IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1:510–514
  Article PubMed CAS Google Scholar
• Chow D, He X, Snow AL, Rose-John S, Garcia KC (2001) Structure of an extracellular gp130 cytokine receptor signaling complex. Science 291:2150–2155
  Article PubMed CAS Google Scholar
• Christadoss P, Poussin M, Deng C (2000) Animal models of myasthenia gravis. Clin Immunol 94:75–87
  Article PubMed CAS Google Scholar
• Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K (1997) Specific inhibition of Stat3 signal transduction by PIAS3. Science 278:1803–1805
  Article PubMed CAS Google Scholar
• Clegg CH, Haugen HS, Rulffes JT, Friend SL, Farr AG (1999) Oncostatin M transforms lymphoid tissue function in transgenic mice by stimulating lymph node T-cell development and thymus autoantibody production. Exp Hematol 27: 712–725
  Article PubMed CAS Google Scholar
• Content J, De Wit L, Poupart P, Opdenakker G, Van Damme J, Billiau A (1985) Induction of a 26-kDaprotein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem 152: 253–257
  Article PubMed CAS Google Scholar
• Dalrymple SA, Slattery R, Aud DM, Krishna M, Lucian LA, Murray R (1996) Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection. Infect Immun 64:3231–3235
  PubMed CAS Google Scholar
• de Hooge AS, van De Loo FA, Arntz OJ, van Den Berg WB (2000) Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. Am J Pathol 157:2081–2091
  PubMed 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
  Article PubMed CAS Google Scholar
• DeChiara TM, Vejsada R, Poueymirou WT, Acheson A, Suri C, Conover JC, Friedman B, McClain J, Pan L, Stahl N, et al. (1995) Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 83:313–322
  Article PubMed CAS Google Scholar
• Deller MC, Hudson KR, Ikemizu S, Bravo J, Jones EY, Heath JK (2000) Crystal structure and functional dissection of the cytostatic cytokine oncostatin M. Structure Fold Des 8:863–874
  Article PubMed CAS Google Scholar
• Deng C, Goluszko E, Tuzun E, Yang H, Christadoss P (2002) Resistance to experimental autoimmune myasthenia gravis in IL-6-deficient mice is associated with reduced germinal center formation and C3 production. J Immunol 169: 1077–1083
  PubMed CAS Google Scholar
• DiCosmo BF, Geba GP, Picarella D, Elias JA, Rankin JA, Stripp BR, Whitsett JA, Flavell RA (1994a) Airway epithelial cell expression of interleukin-6 in transgenic mice. Uncoupling of airway inflammation and bronchial hyperreactivity. J Clin Invest 94:2028–2035
  Article PubMed CAS Google Scholar
• DiCosmo BF, Picarella D, Flavell RA (1994b) Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in nonobese diabetic mice. Int Immunol 6:1829–1837
  Article PubMed CAS Google Scholar
• Diehl S, Anguita J, Hoffmeyer A, Zapton T, Ihle JN, Fikrig E, Rincon M (2000) Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1. Immunity 13:805–815
  Article PubMed CAS Google Scholar
• Diehl S, Chow CW, Weiss L, Palmetshofer A, Twardzik T, Rounds L, Serfling E, Davis RJ, Anguita J, Rincon M (2002) Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. J Exp Med 196: 39–49
  Article PubMed CAS Google Scholar
• Elson GC, Graber P, Losberger C, Herren S, Gretener D, Menoud LN, Wells TN, Kosco-Vilbois MH, Gauchat JF (1998) Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family. J Immunol 161:1371–1379
  PubMed CAS Google Scholar
• Elson GC, Lelievre E, Guillet C, Chevalier S, Plun-Favreau H, Froger J, Suard I, de Coignac AB, Delneste Y, Bonnefoy JY, Gauchat JF, Gascan H (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat Neurosci 3:867–872
  Article PubMed CAS 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
  Article PubMed CAS Google Scholar
• Ernst M, Inglese M, Waring P, Campbell IK, Bao S, Clay FJ, Alexander WS, Wicks IP, Tarlinton DM, Novak U, Heath JK, Dunn AR (2001) Defective gp130-mediated signal transducer and activator of transcription (STAT) signaling results in degenerative joint disease, gastrointestinal ulceration, and failure of uterine implantation. J Exp Med 194:189–203
  Article PubMed CAS Google Scholar
• Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270
  Article PubMed CAS Google Scholar
• Escary JL, Perreau J, Dumenil D, Ezine S, Brulet P (1993) Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 363:361–364
  Article PubMed CAS Google Scholar
• Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A (1998) IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28:2178–2187
  Article PubMed CAS Google Scholar
• Feldmann M, Brennan FM, Maini RN (1996) Rheumatoid arthritis. Cell 85:307–310
  Article PubMed CAS Google Scholar
• Feng GS, Hui CC, Pawson T (1993) SH2-containing phosphotyrosine phosphatase as a target of proteintyrosine kinases. Science 259:1607–1611
  Article PubMed CAS Google Scholar
• Frassanito MA, Cusmai A, Iodice G, Dammacco F (2001) Autocrine interleukin-6 production and highly malignant multiple myeloma: relation with resistance to drug-induced apoptosis. Blood 97:483–489
  Article PubMed CAS Google Scholar
• Fukada T, Hibi M, Yamanaka Y, Takahashi-Tezuka M, Fujitani Y, Yamaguchi T, Nakajima K, Hirano T (1996) Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in antiapoptosis. Immunity 5:449–460
  Article PubMed CAS Google Scholar
• Fukada T, Ohtani T, Yoshida Y, Shirogane T, Nishida K, Nakajima K, Hibi M, Hirano T (1998) STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition. EMBO J 17:6670–6677
  Article PubMed CAS Google Scholar
• Fuller GM, Bunzel RJ, Woloski BM, Nham SU (1987) Isolation of hepatocyte stimulating factor from human monocytes. Biochem Biophys Res Commun 144:1003–1009
  Article PubMed CAS Google Scholar
• Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987) Interferon β2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251–7255
  Article PubMed CAS Google Scholar
• Gerhartz C, Heesel B, Sasse J, Hemmann U, Landgraf C, Schneider-Mergener J, Horn F, Heinrich PC, Graeve L (1996) Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 activation. J Biol Chem 271:12991–12998
  Article PubMed CAS Google Scholar
• Grisius MM, Bermudez DK, Fox PC (1997) Salivary and serum interleukin 6 in primary Sjogren’s syndrome. J Rheumatol 24:1089–1091
  PubMed CAS Google Scholar
• Grotzinger J, Kurapkat G, Wollmer A, Kalai M, Rose-John S (1997) The family of the IL-6-type cytokines: specificity and promiscuity of the receptor complexes. Proteins 27:96–109
  Article PubMed CAS Google Scholar
• Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W (1986) Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem 159:625–632
  Article PubMed CAS Google Scholar
• Heinrich PC, Castell JV, Andus T (1990) Interleukin-6 and the acute phase response. Biochem J 265: 621–636
  PubMed CAS Google Scholar
• Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63:1149–1157
  Article PubMed CAS Google Scholar
• Hibi M, Hirano T (2000) Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors. Leuk Lymphoma 37:299–307
  PubMed CAS Google Scholar
• Hibi M, Hirano T (2001) IL-6 Receptor. In: Oppenheim JJ, Feldman M, Durum SK, Hirano T, Vilcek J, Nicola NA (eds) Cytokine reference. Academic Press, pp 1761–1778 vol 2)
  Google Scholar
• Hirano T, Teranishi T, Toba H, Sakaguchi N, Fukukawa T, Tsuyuguchi I (1981) Human helper T cell factor(s) (ThF). I. Partial purification and characterization. J Immunol 126:517–522
  PubMed CAS Google Scholar
• Hirano T, Teranishi T, Lin B, Onoue K (1984a) Human helper T cell factor(s). IV. Demonstration of a human late-acting B cell differentiation factor acting on Staphylococcus aureus Cowan I-stimulated B cells. J Immunol 133:798–802
  PubMed CAS Google Scholar
• Hirano T, Teranishi T, Onoue K (1984b) Human helper T cell factor(s). III. Characterization of B cell differentiation factor I (BCDF I). J Immunol 132:229–234
  PubMed CAS Google Scholar
• Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490–5494
  Article PubMed CAS Google Scholar
• Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, et al. (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76
  Article PubMed CAS Google Scholar
• Hirano T, Taga T, Yasukawa K, Nakajima K, Nakano N, Takatsuki F, Shimizu M, Murashima A, Tsunasawa S, Sakiyama F, et al. (1987) Human B-cell differentiation factor defined by an antipeptide antibody and its possible role in autoantibody production. Proc Natl Acad Sci USA 84:228–231
  Article PubMed CAS Google Scholar
• Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M, et al. (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18:1797–1801
  Article PubMed CAS Google Scholar
• Hirano T, Taga T, Yamasaki K, Matsuda T, Yasukawa K, Hirata Y, Yawata H, Tanabe O, Akira S, Kishimoto T (1989) Molecular cloning of the cDNAs for interleukin-6/B cell stimulatory factor 2 and its receptor. Ann N Y Acad Sci 557:167–178
  Article PubMed CAS Google Scholar
• Hirano T, Kishimoto T (1990) Interleukin-6. In: Sporn MB, Roberts AB (eds) Handbook of experimental pharmacology. (Peptide growth factors and their receptors vol 95) Springer-Verlag, pp 633–665
  Google Scholar
• Hirano T (1991) Interleukin 6 (IL-6) and its receptor: their role in plasma cell neoplasias. Int J Cell Cloning 9:166–184
  Article PubMed CAS Google Scholar
• Hirano T, Nakajima K, Hibi M (1997) Signaling mechanisms through gp130: a model of the cytokine system. Cytokine Growth Factor Rev 8:241–252
  Article PubMed CAS Google Scholar
• Hirano T (1998) Interleukin 6 and its receptor: ten years later. Int Rev Immunol 16:249–284
  Article PubMed CAS Google Scholar
• Hirano T (1999) Molecular basis underlying functional pleiotropy of cytokines and growth factors. Biochem Biophys Res Commun 260:303–308
  Article PubMed CAS Google Scholar
• Hirano T, Ishihara K, Hibi M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19:2548–2556
  Article PubMed CAS Google Scholar
• Hirano T, Fukada T (2001) IL-6 ligand and receptor family. In: Oppenheim JJ, Feldman M, Durum SK, Hirano T, Vilcek J, Nicola NA (eds) Cytokine reference. (vol 1) Academic Press, pp 523–535
  Google Scholar
• Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y, Ross J, Jr., Muller W, Chien KR (1999) Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97:189–198
  Article PubMed CAS Google Scholar
• Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE (1998) Crystal structure of the tyrosine phosphatase SHP-2. Cell 92:441–450
  Article PubMed CAS Google Scholar
• Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (1996) A Grb2-associated docking protein in EGF-and insulin-receptor signaling. Nature 379:560–564
  Article PubMed CAS Google Scholar
• Holtkamp W, Stollberg T, Reis HE (1995) Serum interleukin-6 is related to disease activity but not disease specificity in inflammatory bowel disease. J Clin Gastroenterol 20:123–126
  Article PubMed CAS Google Scholar
• Ichiba M, Nakajima K, Yamanaka Y, Kiuchi N, Hirano T (1998) Autoregulation of the Stat3 gene through cooperation with a cAMP-responsive element-binding protein. J Biol Chem 273:6132–6138
  Article PubMed CAS Google Scholar
• Ichihara M, Hara T, Kim H, Murate T, Miyajima A (1997) Oncostatin M and leukemia inhibitory factor do not use the same functional receptor in mice. Blood 90:165–173
  PubMed CAS Google Scholar
• Ihara S, Nakajima K, Fukada T, Hibi M, Nagata S, Hirano T, Fukui Y (1997) Dual control of neurite outgrowth by STAT3 and MAP kinase in PC12 cells stimulated with interleukin-6. EMBO J 16:5345–5352
  Article PubMed CAS Google Scholar
• Itoh M, Yoshida Y, Nishida K, Narimatsu M, Hibi M, Hirano T (2000) Role of Gab1 in heart, placenta, and skin development and growth factor-and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol Cell Biol 20:3695–3704
  Article PubMed CAS Google Scholar
• Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC (1992) Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257:88–91
  Article PubMed CAS Google Scholar
• Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM (2001) The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 15:43–58
  Article PubMed CAS Google Scholar
• Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, Fischer M, Neurath MF, Rose-John S (2001) Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem 268: 160–167
  Article PubMed CAS Google Scholar
• Kamimura D, Fu D, Matsuda Y, Atsumi T, Ohtani T, Park SJ, Ishihara K, Hirano T (2002) Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility. Genes Immun 3:136–143
  Article PubMed CAS Google Scholar
• Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, Pfeffer K, Muller M (2000) Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity 13: 549–560
  Article PubMed CAS Google Scholar
• Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, et al. (1988) Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332:83–85
  Article PubMed CAS Google Scholar
• Kawasaki K, Gao YH, Yokose S, Kaji Y, Nakamura T, Suda T, Yoshida K, Taga T, Kishimoto T, Kataoka H, Yuasa T, Norimatsu H, Yamaguchi A (1997) Osteoclasts are present in gp130-deficient mice. Endocrinology 138: 4959–4965
  Article PubMed CAS Google Scholar
• Kim H, Hawley TS, Hawley RG, Baumann H (1998) Protein tyrosine phosphatase 2 (SHP-2) moderates signaling by gp130 but is not required for the induction of acute-phase plasma protein genes in hepatic cells. Mol Cell Biol 18: 1525–1533
  PubMed CAS Google Scholar
• Kim H, Baumann H (1999) Dual signaling role of the protein tyrosine phosphatase SHP-2 in regulating expression of acute-phase plasma proteins by interleukin-6 cytokine receptors in hepatic cells. Mol Cell Biol 19:5326–5338
  PubMed CAS Google Scholar
• Klein B, Zhang XG, Lu ZY, Bataille R (1995) Interleukin-6 in human multiple myeloma. Blood 85:863–872
  PubMed CAS Google Scholar
• Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Kohler G (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342
  Article PubMed CAS Google Scholar
• Kumanogoh A, Marukawa S, Kumanogoh T, Hirota H, Yoshida K, Lee IS, Yasui T, Taga T, Kishimoto T (1997) Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130. Proc Natl Acad Sci USA 94:2478–2482
  Article PubMed CAS Google Scholar
• La Flamme AC, Pearce EJ (1999) The absence of IL-6 does not affect Th2 cell development in vivo, but does lead to impaired proliferation, IL-2 receptor expression, and B cell responses. J Immunol 162:5829–5837
  PubMed Google Scholar
• Le JM, Vilcek J (1989) Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 61:588–602
  PubMed CAS Google Scholar
• Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M, Wendling C, Tomasetto C, Chambon P, Rio MC (1996) Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Science 274: 259–262
  Article PubMed CAS Google Scholar
• Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (2002) SHP2 and SOCS3 contribute to Y759-dependent attenuation of IL-6-signaling through gp130. J Biol Chem 27:27
  Google Scholar
• Lelievre E, Plun-Favreau H, Chevalier S, Froger J, Guillet C, Elson GC, Gauchat JF, Gascan H (2001) Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor αcomponent. J Biol Chem 276:22476–22484
  Article PubMed CAS Google Scholar
• Linker RA, Maurer M, Gaupp S, Martini R, Holtmann B, Giess R, Rieckmann P, Lassmann H, Toyka KV, Sendtner M, Gold R (2002) CNTF is a major protective factor in demyelinating CNS disease: A neurotrophic cytokine as modulator in neuroinflammation. Nat Med 8:620–624
  Article PubMed CAS Google Scholar
• Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K (1998) Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci USA 95:10626–10631
  Article PubMed CAS Google Scholar
• Liu F, Poursine-Laurent J, Wu HY, Link DC (1997) Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation. Blood 90:2583–2590
  PubMed CAS Google Scholar
• Liu Y, Rohrschneider LR (2002) The gift of Gab. FEBS Lett 515:1–7
  Article PubMed CAS Google Scholar
• Liu Z, Simpson RJ, Cheers C (1995) Interaction of interleukin-6, tumor necrosis factor and interleukin-1 during Listeria infection. Immunology 85:562–567
  PubMed CAS Google Scholar
• Lutticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, Harpur AG, Wilks AF, Yasukawa K, Taga T, et al. (1994) Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science 263:89–92
  Article PubMed CAS Google Scholar
• Maddox L, Schwartz DA (2002) The pathophysiology of asthma. Annu Rev Med 53:477–498
  Article PubMed CAS Google Scholar
• Martens AS, Bode JG, Heinrich PC, Graeve L (2000) The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its basolateral sorting in polarized madin-darby canine kidney cells. J Cell Sci 113:3593–3602
  PubMed CAS Google Scholar
• Masu Y, Wolf E, Holtmann B, Sendtner M, Brem G, Thoenen H (1993) Disruption of the CNTF gene results in motor neuron degeneration. Nature 365:27–32
  Article PubMed CAS Google Scholar
• May LT, Helfgott DC, Sehgal PB (1986) Anti-β-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the β2 interferon involved. Proc Natl Acad Sci USA 83:8957–8961
  Article PubMed CAS Google Scholar
• May LT, Ghrayeb J, Santhanam U, Tatter SB, Sthoeger Z, Helfgott DC, Chiorazzi N, Grieninger G, Sehgal PB (1988a) Synthesis and secretion of multiple forms of β2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. J Biol Chem 263:7760–7766
  PubMed CAS Google Scholar
• May LT, Santhanam U, Tatter SB, Bhardwaj N, Ghrayeb J, Sehgal PB (1988b) Phosphorylation of secreted forms of human β2-interferon/hepatocyte stimulating factor/interleukin-6. Biochem Biophys Res Commun 152: 1144–1150
  Article PubMed CAS Google Scholar
• Mihara M, Moriya Y, Kishimoto T, Ohsugi Y (1995) Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor. Br J Rheumatol 34:321–325
  Article PubMed CAS Google Scholar
• Miles SA, Rezai AR, Salazar-Gonzalez JF, Vander Meyden M, Stevens RH, Logan DM, Mitsuyasu RT, Taga T, Hirano T, Kishimoto T, et al. (1990) AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci USA 87:4068–4072
  Article PubMed CAS Google Scholar
• Mitani H, Katayama N, Araki H, Ohishi K, Kobayashi K, Suzuki H, Nishii K, Masuya M, Yasukawa K, Minami N, Shiku H (2000) Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells. Br J Haematol 109:288–295
  Article PubMed CAS Google Scholar
• Molnar EL, Hegyesi H, Toth S, Darvas Z, Laszlo V, Szalai C, Falus A (2000) Biosynthesis of interleukin-6, an autocrine growth factor for melanoma, is regulated by melanoma-derived histamine. Semin Cancer Biol 10:25–28
  Article PubMed CAS Google Scholar
• Moritz RL, Ward LD, Tu GF, Fabri LJ, Ji H, Yasukawa K, Simpson RJ (1999) The N-terminus of gp130 is critical for the formation of the high-affinity interleukin-6 receptor complex. Growth Factors 16:265–278
  Article PubMed CAS Google Scholar
• Moshage H (1997) Cytokines and the hepatic acute phase response. J Pathol 181:257–266
  Article PubMed CAS Google Scholar
• Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T (1988) The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med 167:332–344
  Article PubMed CAS Google Scholar
• Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T (1993) IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260:1808–1810
  Article PubMed CAS 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
  Article PubMed CAS Google Scholar
• Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M, Hirano T (1996) A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J 15: 3651–3658
  PubMed CAS Google Scholar
• Nandurkar HH, Robb L, Tarlinton D, Barnett L, Kontgen F, Begley CG (1997) Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis. Blood 90:2148–2159
  PubMed CAS Google Scholar
• Narazaki M, Witthuhn BA, Yoshida K, Silvennoinen O, Yasukawa K, Ihle JN, Kishimoto T, Taga T (1994) Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130. Proc Natl Acad Sci USA 91:2285–2289
  Article PubMed CAS Google Scholar
• Narimatsu M, Maeda H, Itoh S, Atsumi T, Ohtani T, Nishida K, Itoh M, Kamimura D, Park SJ, Mizuno K, Miyazaki J, Hibi M, Ishihara K, Nakajima K, Hirano T (2001) Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells. Mol Cell Biol 21:6615–6625
  Article PubMed CAS Google Scholar
• Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, Hendrickson SB, Guo HG, Hayward GS, Reitz MS (1997) Kaposi’s sarcoma-associated human herpesvirus-8 encodes homologs of macrophage inflammatory protein-1 and interleukin-6. Nat Med 3:287–292
  Article PubMed CAS 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
  Article PubMed CAS Google Scholar
• Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T (1999) Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T-and B-cell antigen receptors. Blood 93:1809–1816
  PubMed CAS Google Scholar
• Noda M, Takeda K, Sugimoto H, Hosoi T, Takechi K, Hara T, Ishikawa H, Arimura H, Konno K (1991) Purification and characterization of human fibroblast derived differentiation inducing factor for human monoblastic leukemia cells identical to interleukin-6. Anticancer Res 11:961–968
  PubMed CAS Google Scholar
• O’Barr S, Cooper NR (2000) The C5a complement activation peptide increases IL-1β and IL-6 release from amyloid-β-primed human monocytes: implications for Alzheimer’s disease. J Neuroimmunol 109:87–94
  Article PubMed CAS Google Scholar
• O’Brien CA, Manolagas SC (1997) Isolation and characterization of the human gp130 promoter. Regulation by STATS. J Biol Chem 272:15003–15010
  Article PubMed CAS Google Scholar
• Ohshima S, Saeki Y, Mima T, Sasai M, Nishioka K, Nomura S, Kopf M, Katada Y, Tanaka T, Suemura M, Kishimoto T (1998) Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc Natl Acad Sci USA 95:8222–8226
  Article PubMed CAS Google Scholar
• Ohtani T, Ishihara K, Atsumi T, Nishida K, Kaneko Y, Miyata T, Itoh S, Narimatsu M, Maeda H, Fukada T, Itoh M, Okano H, Hibi M, Hirano T (2000) Dissection of signaling cascades through gp130 in vivo: reciprocal roles for STAT3-and SHP2-mediated signals in immune responses. Immunity 12:95–105
  Article PubMed CAS Google Scholar
• Okuda Y, Sakoda S, Bernard CC, Fujimura H, Saeki Y, Kishimoto T, Yanagihara T (1998) IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 10:703–708
  Article PubMed CAS Google Scholar
• Oppenheim RW, Wiese S, Prevette D, Armanini M, Wang S, Houenou LJ, Holtmann B, Gotz R, Pennica D, Sendtner M (2001) Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. J Neurosci 21:1283–1291
  PubMed CAS Google Scholar
• O’Shea JJ, Gadina M, Schreiber RD (2002) Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 109 Suppl:S121–131
  Article PubMed CAS Google Scholar
• Papassotiropoulos A, Hock C, Nitsch RM (2001) Genetics of interleukin 6: implications for Alzheimer’s disease. Neurobiol Aging 22:863–871
  Article PubMed CAS Google Scholar
• Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colamonici OR, van Deursen JM, Grosveld G, Ihle JN (1998) Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93:385–395
  Article PubMed CAS Google Scholar
• Pedersen BK, Steensberg A, Schjerling P (2001) Muscle-derived interleukin-6: possible biological effects. J Physiol 536:329–337
  Article PubMed CAS Google Scholar
• Peters M, Schirmacher P, Goldschmitt J, Odenthal M, Peschel C, Fattori E, Ciliberto G, Dienes HP, Meyer zum Buschenfelde KH, Rose-John S (1997) Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6-sIL-6R double transgenic mice. J Exp Med 185:755–766
  Article PubMed CAS Google Scholar
• Peters M, Muller AM, Rose-John S (1998) Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92:3495–3504
  PubMed CAS Google Scholar
• Poli V, Balena R, Fattori E, Markatos A, Yamamoto M, Tanaka H, Ciliberto G, Rodan GA, Costantini F (1994) Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J 13: 1189–1196
  PubMed CAS Google Scholar
• Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334
  Article PubMed CAS Google Scholar
• Ramsay AJ, Husband AJ, Ramshaw IA, Bao S, Matthaei KI, Koehler G, Kopf M (1994) The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science 264:561–563
  Article PubMed CAS Google Scholar
• Rifas L (1999) Bone and cytokines: beyond IL-1, IL-6 and TNF-α. Calcif Tissue Int 64:1–7
  Article PubMed CAS Google Scholar
• Rincon M, Anguita J, Nakamura T, Fikrig E, Flavell RA (1997) Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J Exp Med 185:461–469
  Article PubMed CAS Google Scholar
• Robb L, Li R, Hartley L, Nandurkar HH, Koentgen F, Begley CG (1998) Infertility in female mice lacking the receptor for interleukin 11 is due to a defective uterine response to implantation. Nat Med 4:303–308
  Article PubMed CAS Google Scholar
• Robledo O, Fourcin M, Chevalier S, Guillet C, Auguste P, Pouplard-Barthelaix A, Pennica D, Gascan H (1997) Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component. J Biol Chem 272: 4855–4863
  Article PubMed CAS Google Scholar
• Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D, Johnson EM Jr, Schreiber RD (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 93:373–383
  Article PubMed CAS Google Scholar
• Romani L, Mencacci A, Cenci E, Spaccapelo R, Toniatti C, Puccetti P, Bistoni F, Poli V (1996) Impaired neutrophil response and CD4+ T helper cell 1 development in interleukin 6-deficient mice infected with Candida albicans. J Exp Med 183:1345–1355
  Article PubMed CAS Google Scholar
• Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A (1997) Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6:315–325
  Article PubMed CAS Google Scholar
• Saito M, Yoshida K, Hibi M, Taga T, Kishimoto T (1992) Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. J Immunol 148:4066–4071
  PubMed CAS Google Scholar
• Samoilova EB, Horton JL, Hilliard B, Liu TS, Chen Y (1998) IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 161:6480–6486
  PubMed CAS Google Scholar
• Santhanam U, Ray A, Sehgal PB (1991) Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Proc Natl Acad Sci USA 88:7605–7609
  Article PubMed CAS Google Scholar
• Sasai M, Saeki Y, Ohshima S, Nishioka K, Mima T, Tanaka T, Katada Y, Yoshizaki K, Suemura M, Kishimoto T (1999) Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice. Arthritis Rheum 42:1635–1643
  Article PubMed CAS Google Scholar
• Schaper F, Gendo C, Eck M, Schmitz J, Grimm C, Anhuf D, Kerr IM, Heinrich PC (1998) Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression. Biochem J 335:557–565
  PubMed CAS Google Scholar
• Schirmacher P, Peters M, Ciliberto G, Blessing M, Lotz J, Meyer zum Buschenfelde KH, Rose-John S (1998) Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. Am J Pathol 153:639–648
  PubMed CAS Google Scholar
• Schmitz J, Dahmen H, Grimm C, Gendo C, Muller-Newen G, Heinrich PC, Schaper F (2000a) The cytoplasmic tyrosine motifs in full-length glycoprotein 130 have different roles in IL-6 signal transduction. J Immunol 164: 848–854
  PubMed CAS Google Scholar
• Schmitz J, Weissenbach M, Haan S, Heinrich PC, Schaper F (2000b) SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130. J Biol Chem 275:12848–12856
  Article PubMed CAS Google Scholar
• Schreiber M, Kolbus A, Piu F, Szabowski A, Mohle-Steinlein U, Tian J, Karin M, Angel P, Wagner EF (1999) Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev 13:607–619
  Article PubMed CAS Google Scholar
• Sehgal PB, Grienger G, Tosato G (1989) Regulation of the acute phase and immune responses: interleukin-6. Ann N Y Acad Sci 557:1–583
  Google Scholar
• Senaldi G, Stolina M, Guo J, Faggioni R, McCabe S, Kaufman SA, Van G, Xu W, Fletcher FA, Boone T, Chang MS, Sarmiento U, Cattley RC (2002) Regulatory effects of novel neurotrophin-1/b cell-stimulating factor-3 (cardiotrophin-like cytokine) on B cell function. J Immunol 168:5690–5698
  PubMed CAS Google Scholar
• Shen MM, Skoda RC, Cardiff RD, Campos-Torres J, Leder P, Ornitz DM (1994) Expression of LIF in transgenic mice results in altered thymic epithelium and apparent interconversion of thymic and lymph node morphologies. EMBO J 13:1375–1385
  PubMed CAS Google Scholar
• Shimoda K, Kato K, Aoki K, Matsuda T, Miyamoto A, Shibamori M, Yamashita M, Numata A, Takase K, Kobayashi S, Shibata S, Asano Y, Gondo H, Sekiguchi K, Nakayama K, Nakayama T, Okamura T, Okamura S, Niho Y (2000) Tyk2 plays a restricted role in IFN α signaling, although it is required for IL-12-mediated T cell function. Immunity 13: 561–571
  Article PubMed CAS Google Scholar
• Shirogane T, Fukada T, Muller JM, Shima DT, Hibi M, Hirano T (1999) Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity 11:709–719
  Article PubMed CAS Google Scholar
• Shirota K, LeDuy L, Yuan SY, Jothy S (1990) Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. Virchows Arch B Cell Pathol Incl Mol Pathol 58:303–308
  Article PubMed CAS Google Scholar
• Smith PC, Hobisch A, Lin DL, Culig Z, Keller ET (2001) Interleukin-6 and prostate cancer progression. Cytokine Growth Factor Rev 12:33–40
  Article PubMed CAS Google Scholar
• Somers W, Stahl M, Seehra JS (1997) 1. 9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J 16:989–997
  Article PubMed CAS Google Scholar
• Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, et al. (1993) SH2 domains recognize specific phosphopeptide sequences. Cell 72:767–778
  Article PubMed CAS Google Scholar
• Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, et al. (1994) Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 β receptor components. Science 263:92–95
  Article PubMed CAS Google Scholar
• Stahl N, Farruggella TJ, Boulton TG, Zhong Z, Darnell JE, Jr., Yancopoulos GD (1995) Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science 267:1349–1353
  Article PubMed CAS 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 signaling. Nature 387:917–921
  Article PubMed CAS Google Scholar
• Stelmasiak Z, Koziol-Montewka M, Dobosz B, Rejdak K, Bartosik-Psujek H, Mitosek-Szewczyk K, Belniak-Legiec E (2000) Interleukin-6 concentration in serum and cerebrospinal fluid in multiple sclerosis patients. Med Sci Monit 6: 1104–1108
  PubMed CAS Google Scholar
• Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, Abbondanzo SJ (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359:76–79
  Article PubMed CAS Google Scholar
• Stuart RA, Littlewood AJ, Maddison PJ, Hall ND (1995) Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders. Clin Exp Rheumatol 13:17–22
  PubMed CAS Google Scholar
• Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, Miyazaki J, Yamamura K, Hirano T, Kishimoto T (1989) IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 86:7547–7551
  Article PubMed CAS Google Scholar
• Suematsu S, Matsusaka T, Matsuda T, Ohno S, Miyazaki J, Yamamura K, Hirano T, Kishimoto T (1992) Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 89:232–235
  Article PubMed CAS Google Scholar
• Suzuki A, Hanada T, Mitsuyama K, Yoshida T, Kamizono S, Hoshino T, Kubo M, Yamashita A, Okabe M, Takeda K, Akira S, Matsumoto S, Toyonaga A, Sata M, Yoshimura A (2001) CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J Exp Med 193:471–481
  Article PubMed CAS Google Scholar
• Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573–581
  Article PubMed CAS Google Scholar
• Takahashi-Tezuka M, Yoshida Y, Fukada T, Ohtani T, Yamanaka Y, Nishida K, Nakajima K, Hibi M, Hirano T (1998) Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase. Mol Cell Biol 18:4109–4117
  PubMed CAS Google Scholar
• Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S (1998) Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol 161:4652–4660
  PubMed CAS Google Scholar
• Tanaka M, Kishimura M, Ozaki S, Osakada F, Hashimoto H, Okubo M, Murakami M, Nakao K (2000) Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies in rheumatoid arthritis. J Clin Invest 106: 137–144
  Article PubMed CAS Google Scholar
• Tanaka T, Katada Y, Higa S, Fujiwara H, Wang W, Saeki Y, Ohshima S, Okuda Y, Suemura M, Kishimoto T (2001) Enhancement of T helper2 response in the absence of interleukin (IL-)6; an inhibition of IL-4-mediated T helper2 cell differentiation by IL-6. Cytokine 13:193–201
  Article PubMed CAS Google Scholar
• Tebbutt NC, Giraud AS, Inglese M, Jenkins B, Waring P, Clay FJ, Malki S, Alderman BM, Grail D, Hollande F, Heath JK, Ernst M (2002) Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 8:1089–1097
  Article PubMed CAS Google Scholar
• ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M, Shuai K (2002) Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 22:5662–5668
  Article PubMed CAS Google Scholar
• Teranishi T, Hirano T, Arima N, Onoue K (1982) Human helper T cell factor(s) (ThF). II. Induction of IgG production in B lymphoblastoid cell lines and identification of T cell-replacing factor-(TRF) like factor(s). J Immunol 128: 1903–1908
  PubMed CAS Google Scholar
• Tonouchi N, Oouchi N, Kashima N, Kawai M, Nagase K, Okano A, Matsui H, Yamada K, Hirano T, Kishimoto T (1988) High-level expression of human BSF-2/IL-6 cDNA in Escherichia coli using a new type of expression-preparation system. J Biochem (Tokyo) 104:30–34
  CAS Google Scholar
• Tsunenari T, Koishihara Y, Nakamura A, Moriya M, Ohkawa H, Goto H, Shimazaki C, Nakagawa M, Ohsugi Y, Kishimoto T, Akamatsu K (1997) New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor. Blood 90:2437–2444
  PubMed CAS Google Scholar
• Udagawa N, Takahashi N, Katagiri T, Tamura T, Wada S, Findlay DM, Martin TJ, Hirota H, Taga T, Kishimoto T, et al. (1995) Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J Exp Med 182:1461–1468
  Article PubMed CAS Google Scholar
• Ueda T, Bruchovsky N, Sadar MD (2002) Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 277:7076–7085
  Article PubMed CAS Google Scholar
• Uozumi H, Hiroi Y, Zou Y, Takimoto E, Toko H, Niu P, Shimoyama M, Yazaki Y, Nagai R, Komuro I (2001) gp130 plays a critical role in pressure overload-induced cardiac hypertrophy. J Biol Chem 276:23115–23119
  Article PubMed CAS Google Scholar
• Van Snick J, Cayphas S, Szikora JP, Renauld JC, Van Roost E, Boon T, Simpson RJ (1988) cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol 18:193–197
  Article PubMed Google Scholar
• Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278
  Article PubMed Google Scholar
• Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J (1988) B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol 18: 607–612
  Article PubMed CAS Google Scholar
• Vogel W, Lammers R, Huang J, Ullrich A (1993) Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science 259:1611–1614
  Article PubMed CAS Google Scholar
• Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO (2002a) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565
  Article PubMed CAS Google Scholar
• Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO (2002b) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79
  Article PubMed CAS Google Scholar
• Wang J, Homer RJ, Chen Q, Elias JA (2000a) Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation. J Immunol 165:4051–4061
  PubMed CAS Google Scholar
• Wang J, Homer RJ, Hong L, Cohn L, Lee CG, Jung S, Elias JA (2000b) IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production. J Immunol 165:2222–2231
  PubMed CAS Google Scholar
• Wang YD, Gu ZJ, Huang JA, Zhu YB, Zhou ZH, Xie W, Xu Y, Qiu YH, Zhang XG (2002) gp130-linked signal transduction promotes the differentiation and maturation of dendritic cells. Int Immunol 14:599–603
  Article PubMed CAS Google Scholar
• Ward LD, Howlett GJ, Discolo G, Yasukawa K, Hammacher A, Moritz RL, Simpson RJ (1994) High affinity interleukin-6 receptor is a hexameric complex consisting of two molecules each of interleukin-6, interleukin-6 receptor, and gp-130. J Biol Chem 269:23286–23289
  PubMed CAS Google Scholar
• Ware CB, Horowitz MC, Renshaw BR, Hunt JS, Liggitt D, Koblar SA, Gliniak BC, McKenna HJ, Papayannopoulou T, Thoma B, et al. (1995) Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 121:1283–1299
  PubMed CAS Google Scholar
• Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M (1980) Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci USA 77:7152–7156
  Article PubMed CAS Google Scholar
• Wolf I, Jenkins BJ, Liu Y, Seiffert M, Custodio JM, Young P, Rohrschneider LR (2002) Gab3, a new DOS/Gab family member, facilitates macrophage differentiation. Mol Cell Biol 22:231–244
  Article PubMed CAS Google Scholar
• Wong CK, Ho CY, Ko FW, Chan CH, Ho AS, Hui DS, Lam CW (2001) Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 125: 177–183
  Article PubMed CAS Google Scholar
• Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei X-F, Achong M (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J. Clin. Invest. 101:311–320
  Article PubMed CAS Google Scholar
• Yamanaka Y, Nakajima K, Fukada T, Hibi M, Hirano T (1996) Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation. EMBO J 15:1557–1565
  PubMed CAS Google Scholar
• Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFN β 2) receptor. Science 241:825–828
  Article PubMed CAS Google Scholar
• Yasukawa H, Sasaki A, Yoshimura A (2000) Negative regulation of cytokine signaling pathways. Annu Rev Immunol 18:143–164
  Article PubMed CAS Google Scholar
• Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J 6:2939–2945
  PubMed CAS Google Scholar
• Yokoyama A, Kohno N, Fujino S, Hamada H, Inoue Y, Fujioka S, Ishida S, Hiwada K (1995) Circulating interleukin-6 levels in patients with bronchial asthma. Am J Respir Crit Care Med 151:1354–1358
  PubMed CAS Google Scholar
• Yoshida K, Taga T, Saito M, Suematsu S, Kumanogoh A, Tanaka T, Fujiwara H, Hirata M, Yamagami T, Nakahata T, Hirabayashi T, Yoneda Y, Tanaka K, Wang WZ, Mori C, Shiota K, Yoshida N, Kishimoto T (1996) Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc Natl Acad Sci USA 93:407–411
  Article PubMed CAS Google Scholar
• Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T, et al. (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74: 1360–1367
  PubMed CAS Google Scholar
• Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214
  Article PubMed CAS Google Scholar
• Zhang JG, Zhang Y, Owczarek CM, Ward LD, Moritz RL, Simpson RJ, Yasukawa K, Nicola NA (1998) Identification and characterization of two distinct truncated forms of gp130 and a soluble form of leukemia inhibitory factor receptor α-chain in normal human urine and plasma. J Biol Chem 273:10798–10805
  Article PubMed CAS Google Scholar
• Zhong J, Dietzel ID, Wahle P, Kopf M, Heumann R (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19:4305–4313
  PubMed CAS Google Scholar
• Zhu M, Oishi K, Lee SC, Patterson PH (2001) Studies using leukemia inhibitory factor (LIF) knockout mice and a LIF adenoviral vector demonstrate a key anti-inflammatory role for this cytokine in cutaneous inflammation. J Immunol 166:2049–2054
  PubMed CAS Google Scholar
• Zilberstein A, Ruggieri R, Korn JH, Revel M (1986) Structure and expression of cDNA and genes for human interferon-β-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J 5:2529–2537
  PubMed CAS Google Scholar

Download references