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Physiological and pathological role of gp130, a common signal transducer for IL-6-family of cytokines

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Bone Marrow Transplantation

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Summary

Receptor complexes for interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), oncostatin M (OM), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT-1) utilize membrane glycoprotein gp130 as a common signal-transducing component. In order to investigate detailed physiological roles of gp130 and to determine pathological consequences of complete lack or abnormal activation of gp130, mice deficient for gp130 protein or expressing continuously activated gp130 protein have been made. A gp130 null mutation is lethal, and embryos deficient for gp130 protein progressively die between 12.5 days post coitum (dpc) and term. They show, at 16.5 dpc, hypoplastic development of the ventricular myocardium. They have greatly reduced numbers of pluripotential and committed hematopoietic progenitors in the liver, as measured on 13.5 dpc. gp130- / - placentas on and after 14.5 dpc are smaller than controls and exhibit impaired maternofetal transport. Continuous activation of gp130 in vivo by overexpressing both IL-6 and IL-6R leads to hypertrophy of ventricular myocardium and thickened ventricular walls of the heart in adulthood. These results indicate crucial roles of gp 130 in cardiomyocyte regulation, hematopoiesis, and placental development.

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References

  1. Bazan JF(1990) Structural design and molecular evolution of a cytokine receptor superfamily. Proc Nail Acad Sci USA 87:6934–6938

    Article  CAS  Google Scholar 

  2. Taga T, and Kishimoto T (1992) Cytokine receptors and signal transduction. FASEB J 6: 3387–3396

    Google Scholar 

  3. Kishimoto T, Taga T, and Akira S (1994) Cytokine signal transduction. Cell 76: 253–262

    Article  PubMed  CAS  Google Scholar 

  4. Taga T, Narazaki M, Yasukawa K, Saito T, Miki D, Hamaguchi M, Davis S, Shoyab M, Yancopoulos GD, and Kishimoto T (1992) Functional inhibition of hematopoietic and neurotrophic cytokines by blocking the interleukin 6 signal transducer gp130. Proc Natl Acad Sci USA 89: 10998–11001

    Article  PubMed  CAS  Google Scholar 

  5. Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren J, Yasukawa K, Kishimoto T, Anderson DJ, Stahl N, and Yancopoulos GD (1992) CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell 69: 1121–1132

    Article  PubMed  CAS  Google Scholar 

  6. Gearing DP, Comeau MR, Friend DJ, Gimpel SD, Thut Cl, McGourty J, Brasher KK, King JA, Gillis S, Mosley B, Ziegler SF, and Cosman D (1992) The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the L1F receptor. Science 255: 1434–1437

    Article  PubMed  CAS  Google Scholar 

  7. Liu J, Modrell B, Aruffo A, Marken JS, Taga T, Yasukawa K, Murakami M, Kishimoto T, and Shoyab M (1992) Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. J BiolChem 267: 16763–16766

    Google Scholar 

  8. Yin T, Taga T, Tsang ML-S, Yasukawa K, Kishimoto T, Yang Y-C (1993) Involvement of interleukin-6 signal transducer gp130 in interleukin-l1-mediated signal transduction. J Immunol 151: 2555–2561

    PubMed  CAS  Google Scholar 

  9. Pennica D, Shaw KJ, Swanson TA, Moore MW, Sheliton DL, Zioncheck KA, Rosenthal A, Taga T, Paoni NF, and Wood WI (1995) Cardiotropin-1: Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. J BiolChem 270: 10915–10922

    Google Scholar 

  10. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, and 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 

  11. Hibi M, Murakami M, Saito M, Hirano T, Taga T, and Kishimoto T (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63: 1149–1157

    Article  PubMed  CAS  Google Scholar 

  12. Kishimoto T, Akira S, and Taga T (1992) Interleukin-6 and its receptor: A paradigm for cytokines. Science 258: 593–597

    Google Scholar 

  13. Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, and 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 

  14. Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, and Yancopoulos GD (1993) LIFRB and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260: 1805–1808

    Article  PubMed  CAS  Google Scholar 

  15. Murakami-Mori K, Taga T, Kishimoto T, and Nakamura S (1995) AIDS-associated Kaposi s sarcoma (KS) cells express oncostatin M (OM)-specific receptor but not leukemia inhibitory facotr/OM receptor or interleukin-6 receptor. J Clin Invest 96: 1319–1327

    Article  PubMed  CAS  Google Scholar 

  16. Hilton DJ, Hilton AA, Raicevic A, Rakar S, Harrison-Smith M, Gough NM, Begley CG, Metcalf D, Nicola NA, and Willson TA (1994) Cloning of a murine IL-11 receptor a chain; requirement for gp130 high affinity binding and signal transduction. EMBO. 1 13: 4765–4775

    Google Scholar 

  17. Narazaki M, Witthuhn BA, Yoshida K, Silvennoinen O, Yasukawa K, Ihle JN, Kishimoto T, and Taga T (1994) Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130. Proc Nati Acad Sci USA 91: 2285–2289

    Article  CAS  Google Scholar 

  18. Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, Ihle JN, Yancopoulos GD (1994) Association and activation of JakTyk kinases by CNTF-LIF-OSM-IL-6 b receptor components. Science 263: 92–95

    Article  PubMed  CAS  Google Scholar 

  19. Stahl N, Farruggella J, Boulton T, G Zhong, Z Darnel, JE 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 

  20. Akira S, Nishio Y, Inoue M, Wang X-J, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, and Kishimoto T (1994) Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77: 63–71

    Article  PubMed  CAS  Google Scholar 

  21. Lütticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, Harpur AG, Wilks AF, Yasukawa K, Taga T, Kishimoto T, Barbieri G, Pellegrini S, Sendtner M, Heinrich PC, Horn F (1994) Association of transcription factor APRF and protein kinase Jakl with the interleukin-6 signal transducer gp130. Science 263: 89–92

    Article  PubMed  Google Scholar 

  22. Wegenka UM, Lütticken C, Buschmann J, Yuan J, Lottspeich F, Müller-Esterl W, Schindler C, Roeb E, Heinrich PC, Horn F (1994) The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription ( STAT) family. Mol Cell Biol 14: 3186–3196

    Google Scholar 

  23. Zhang X, Blenis J, Li H-C, Schindler C, Chen-Kiang S (1995) Requirement of serine phosphorylation for formation of STAT-promoter complexes. Science 267: 1990–1994

    Article  PubMed  CAS  Google Scholar 

  24. Boulton TG, Zhong Z, Wen Z, Darnell JEJr, Stahl N, and Yancopoulos GD (1995) STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7-sensitive kinase. Proc Natl Acad Sci USA 92: 6915–6919

    Article  PubMed  CAS  Google Scholar 

  25. Wen Z, Zhong Z, and Darnell JEJr (1995) Maximal activation of transcription by Statl and Stat3 requires both tyrosine and serine phosphorylation. Cell 82: 241–250

    Article  PubMed  CAS  Google Scholar 

  26. Satoh T, Nakafuku M, and Kajiro Y (1992) Function of Ras as a molecular switch in signal transduction. J Biol Chem 267: 24149–24153

    PubMed  CAS  Google Scholar 

  27. Boulton TG, Stahl N, and Yancopoulos GD (1994) Ciliary neurotrophic factor/ leukemia inhibitory factor/ interleukin 6/ oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors. J Biol Chem 269: 11648–11655

    PubMed  CAS  Google Scholar 

  28. Daeipour M, Kumar G, and Amaral MC (1993) Recombinant IL-6 activates p42 and p44 mitogen-activated protein kinases in the IL-6 responsive B cell line, AF-10. J Immunol 150: 4743–4753

    CAS  Google Scholar 

  29. Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T, and Akira S (1993) Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL-6. Proc Natl Acad Sci USA 90: 2207–2211

    Article  PubMed  CAS  Google Scholar 

  30. Saito M, Yoshida K, Hibi M, Taga T, and 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 

  31. 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 W-Z, Mori C, Shiota K, Yoshida N, and Kishimoto T (in press) Targeted disruption of gp130, a common signal transducer for IL-6-family of cytokines, leads to myocardial and hematological disorders. Proc Natl Acad Sci USA

    Google Scholar 

  32. Rumyantsev PP (1977) Interaction of proliferation and differentiation processes during cardiac myogenesis and regulation. Int Rev Cytol 91: 187–273

    Article  Google Scholar 

  33. Yasukawa K, Saito T, Fukunaga T, Sekimori Y, Koishikawa T, Fukui H, Ohsugi Y, Matsuda T, Yawata H, Hirano T, Taga T, and Kishimoto T (1990) Purification and characterization of soluble human IL-6 receptor expressed in CHO cell. J Biochem 108: 673–676

    PubMed  CAS  Google Scholar 

  34. Pennica D, King K, Shaw KJ, Luis E, Rullamas J, Luoh S-M, Darbonne WC, Knutzon DS, Yen R, Chien KR, Baker JB, and Wood W (1995) Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci USA 92: 1142–1146

    Article  PubMed  CAS  Google Scholar 

  35. Hirota H, Yoshida K, Kishimoto T, and Taga T (1995) Continuous activation of gp130, a signal transducing receptor component for interleukin6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 92: 4862–4866

    Article  PubMed  CAS  Google Scholar 

  36. Ware CB, Horowitz MC, Renshaw BR, Hunt JS, Liggitt D, Koblar SA, Gliniak BC, McKenna RI, Papayannopoulos T, Thoma B, Cheng L, Donovan PJ, Peschon JJ, Bartlett PF, Willis CR, Wright BD, Carpenter MK, Davison BL, and Gearing DP (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 

  37. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Köntgen F and Abbondanzo, JS (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359: 76–79

    Article  PubMed  CAS  Google Scholar 

  38. Escary J, Perreau J, Duménil D, Ezine S, and Brûlet 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 

  39. Nishino E, Matsuzaki N, Masuhiro K, Kameda T, Taniguchi T, Takagi T, Sagi F, and Tanizawa O (1989) Trophoblast-derived Interleukin-6 (IL-6) regulates human chorionic gonadotropin release through IL-6 receptor on human trophoblasts. J Clin Endocrinol Metabol 71: 536–541

    Google Scholar 

  40. Yamaguchi M, Ogren L, Endo H, Thordarson G, Kensinger R, and Talamantes F (1993) Interleukin-6 inhibits mouse placental lactogen-II but not mouse placental lactogen-I secretion in vitro. Proc Natl Acad Sci USA 90: 11905–11909

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565, Japan

    Tetsuya Taga, Kanji Yoshida & Hisao Hirota

  2. Department of Medicine III, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan

    Hisao Hirota & Tadamitsu Kishimoto

Authors
  1. Tetsuya Taga
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  2. Kanji Yoshida
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  3. Hisao Hirota
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  4. Tadamitsu Kishimoto
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Editor information

Editors and Affiliations

  1. First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570, Japan

    Susumu Ikehara M.D., Ph.D. (Professor) (Professor)

  2. International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162, Japan

    Fumimaro Takaku M.D., Ph.D. (President) (President)

  3. Department of Pediatrics, All Children’s Hospital, University of South Florida, 801 Sixth Street South, Box 753, St. Petersburg, FL, 33701, USA

    Robert A. Good M.D., Ph.D., D.Sc., FACP (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology) (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology)

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© 1996 Springer-Verlag Tokyo

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Taga, T., Yoshida, K., Hirota, H., Kishimoto, T. (1996). Physiological and pathological role of gp130, a common signal transducer for IL-6-family of cytokines. In: Ikehara, S., Takaku, F., Good, R.A. (eds) Bone Marrow Transplantation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68320-9_13

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  • DOI: https://doi.org/10.1007/978-4-431-68320-9_13

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68322-3

  • Online ISBN: 978-4-431-68320-9

  • eBook Packages: Springer Book Archive

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