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Functional roles of glycans for interaction between cytokines and receptors

Research Project

Project/Area Number 14082208
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Institute of Technology (2006)
Sasaki Institute (2002-2005)

Principal Investigator

YAMASHITA Katsuko  Tokyo Institute of Technology, Innovative Research Initiatives, Professor (70030905)

Project Period (FY) 2002 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥76,100,000 (Direct Cost: ¥76,100,000)
Fiscal Year 2006: ¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2005: ¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2004: ¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2003: ¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2002: ¥11,300,000 (Direct Cost: ¥11,300,000)
Keywordshigh-affinity complex formation / GPI-anchored glycan / High-mannose type glycan / cytokine receptor glycan / IL-2 / IL-18 / TNF-α / carbohydrate recognition activity / IL-8 / チロシンリン酸化 / ガレクチン-4 / 硫酸化コレステロール / アポトーシス / リソソーム酵素分泌 / 硫酸化糖脂質 / IL-6 / HepG2細胞 / フィブリノーゲン / IL-6受容体 / gp130 / CD48 / IL-18受容体 / サイトカイン / GPI-アンカー糖鎖 / マンノース6リン酸 / 糖鎖認識 / マンノビオースジリン酸
Research Abstract

Many cytokines recognize unique carbohydrate sequences of various glycoconjugates. Although their functional roles mostly remain to be identified to date, fibroblast growth factor (FGF) had been clearly demonstrated in relation to the physiological activities. We found in this project that various cytokines recognize high-mannose type glycans or GPI-anchor glycans, and following high affinity complex formation with receptor subunits triggers various physiological activities as follows, 1) interleukin-2 (IL-2) binds to both high-mannnose type glycan and a specific peptide sequence in IL-2 receptor α (IL-2Rα), and triggers the formation of high-affinity octamer, (IL-2)_2(IL-2Rα)_2β_2γ_2, and immediately induces cell proliferation. Similar mechanisms were also found to IL-5, IL-6, and IL-8. 2) There exists a group of glycosylphosphatidyl inositol(GPI)-anchored glycan recognizing cytokines, including TNF-α, TNF-β, IL-1β, and IL-18. Interleukin-18 (IL-18) and IL-18 receptor α (IL-18Rα) recognize the distinct GPI-anchored glycan portion of CD48, and the high-affinity octamer formation of (IL-18)_2(CD48)_2(IL-18Rα)_2(IL-18Rβ)_2 triggers the intracellular signal transduction and produces interferon-γ in KG-1 cells. Tumor necrosis factor-α (TNF-α) binds to TNF-α receptor and the second mannose-6-phosphate diester in GPI-anchor glycan. The addition of mmanose-6-phosphate or PI-PLC-treatment on U937 cells diminishes TNF-α inducing apoptosis, indicating that the formation of nanomer, (TNF-α)_3(GPI-glycan)_3(TNFR)_3 triggers various physiological actions. As the results, it was elucidated that such rigid-oligomerization between cytokines and their receptor subunits via the specific glycans is important to modulate immunological response.

Report

(6 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (60 results)

All 2007 2006 2005 2004 2003 2002 Other

All Journal Article (30 results) Book (5 results) Publications (25 results)

  • [Journal Article] Recognition mechanism of galectin-4 for sulfated compounds2007

    • Author(s)
      Ideo, H., Seko, A., Yamashita, K.
    • Journal Title

      J. Biol. Chem 282

      Pages: 21081-21089

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recognition mechanism of galectin-4 for sulfated compounds2007

    • Author(s)
      Ideo, H., Seko, A., Yamashita, K.
    • Journal Title

      J. Biol, Chem. 282

      Pages: 21081-21089

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] サイトカインの糖鎖認識と生理機能発現への関与2007

    • Author(s)
      福島 慶子
    • Journal Title

      「実験医学」(波及する糖鎖研究) (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CEAの糖鎖を介した多様な機構2007

    • Author(s)
      山下 克子
    • Journal Title

      日本臨床検査自動化学会会誌 (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structures of carbohydrate recognition domain of Ca^<2+>-independent cargo receptors Emp46p and Emp47p.2006

    • Author(s)
      Satoh, T.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 10410-10419

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ectopical Expression of a N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinoma.2006

    • Author(s)
      Kanoh, A.
    • Journal Title

      Glycoconjugate J. 23

      Pages: 453-460

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Essential roles of 3'-Phosphoadenosine 5'-Phosphosulfate (PAPS) synthase in embryonic and lary development of the nematode Caenorhabditis elegans.2006

    • Author(s)
      Dejima, K.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 11431-11440

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structures of carbohydrate recognition domain of Ca^<2+>-independent cargo receptors Emp46p and Emp47p.2006

    • Author(s)
      Satoh, T.
    • Journal Title

      J.Biol.Chem., (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ectopical Expression of a N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinoma.2006

    • Author(s)
      Kanoh, A.
    • Journal Title

      Glycoconjugate J., (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Essential roles of 3'-Phosphoadenosine 5'-Phosphosulfate (PAPS) synthase in embryonic and larval development of the nematode Caenorhabditis elegans.,2006

    • Author(s)
      Dejima, K.
    • Journal Title

      J.Biol.Chem (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification and characterization of a novel galactose : β1, 3-N-acetylglucosaminyltransferase (β3Gn-T8).2005

    • Author(s)
      Seko, A., Yamashita, K
    • Journal Title

      Glycobiology 15

      Pages: 943-951

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional role played by the GPI-anchor glycan of CD48 in IL-18-induced IFN-gamma production.2005

    • Author(s)
      Fukushima, K., Ikehara, Y., Yamashita, K.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 18056-18062

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification and characterization of a novel galactose : β1,3-N-acetylglucosaminyltransferase (β3Gn-T8).2005

    • Author(s)
      Seko, A., Yamashita, K.
    • Journal Title

      Glycobiology 15

      Pages: 943-951

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] dentification and characterization of a novel galactose : β1,3-N-acetylglucosaminyltransferase (β3Gn-T8).2005

    • Author(s)
      Seko, A.
    • Journal Title

      Glycobiology 15

      Pages: 943-951

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Porcine, mouse, and human Gal 3-O-sulfotransferase-2 enzymes have different substrate specificities ; the porcine enzyme requires basic compounds for its catalytic activity.2005

    • Author(s)
      Seko, A.
    • Journal Title

      Biochemical Journal 391

      Pages: 77-85

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Functional role played by the GPI-anchor glycan of CD48 in IL-18-induced IFN-gamma production.2005

    • Author(s)
      Fukushima, K.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 18056-18062

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Galectin-4 binds to sulfated glycosphingolipids and CEA in patches on the cell surface of human colon adenocarcinoma cells.2005

    • Author(s)
      Ideo, H.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 4730-4737

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Functional role played by the GPI-anchor glycan of CD48 in IL-18-induced IFN-gamma production.2005

    • Author(s)
      Fukushima, K., Ikehara, Y., Yamashita, K.
    • Journal Title

      J.Biol.Chem. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification and characterization of a novel galactose: β1,3-N-acetylglucosaminyltransferase (β3Gn-T8):2005

    • Author(s)
      Seko, A., Yamashita, K.
    • Journal Title

      Glycobiology 15(In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Porcine, mouse, and human Gal 3-O-sulfotransferase-2 enzymes have different substrate specificities.2005

    • Author(s)
      Seko, A., Sumiya, J., Yamashita, K
    • Journal Title

      BIochem.J. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Galectin-4 binds to sulfated glycosphingolipids and carcinoembryonic antigen in patches on the cell surface of human colon.2005

    • Author(s)
      Ideo, H., Seko, A., Yamashita, K.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 4730-4737

    • Related Report
      2004 Annual Research Report
  • [Journal Article] GPI-anchor recognition of TNF-α modulates apoptosis of U937 cells.2004

    • Author(s)
      Fukushima, K., Ishiyama, C, Yamashita, K.
    • Journal Title

      Arch. Biochem. Biophys. 426

      Pages: 298-305

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The carbohydrate recognition by cytokines modulates their physiological activities.2004

    • Author(s)
      Fukushima, K., Yamashita, K.
    • Journal Title

      Glycoconj J. 21

      Pages: 31-34

    • Related Report
      2004 Annual Research Report
  • [Journal Article] GPI-anchor recognition of TNF-α modulates apoptosis of U937 cells.2004

    • Author(s)
      Fukushima, K., Ishiyama, C., Yamashita, K.
    • Journal Title

      Arch.Biochem.Biophys. 426

      Pages: 298-305

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The binding of VIP36 and α-amylase in the secretory vesicles via high mannose-type glycans.2004

    • Author(s)
      Hara-Kuge, S., Seko, A., Yamashita, K.et al.
    • Journal Title

      Glycobiology 14

      Pages: 739-744

    • Related Report
      2004 Annual Research Report
  • [Journal Article] β1,3-N-acetylglucosaminyltransferase-7 (βGn-T7) acts efficiently on keratan sulfate-related glycans.2004

    • Author(s)
      Seko, A., Yamashita, K.
    • Journal Title

      FEBS Lett. 556

      Pages: 216-222

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Aβ-N-acetylglucosaminyl phosphate diester residue is attached to the glycosyl-phosphatidylinositol (GPI) anchor of human placental alkaline phosphatase : a target of the channel-forming toxin aerolysin2003

    • Author(s)
      Fukushima, K., Ikehara, Y., Kanai, M., Kochibe, N., Kuroki, M., Yamashita, K.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 36296-36303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A β-N-acetylglucosaminyl phosphate diester residue is attached to the glycosyl-phosphatidyhnositol (GPI) anchor of human placental alkaline phosphatase : a target of the channel-forming toxin aerolysin2003

    • Author(s)
      Fukushima, K., Ikehara, Y., Kanai, M., Kochibe, N., Kuroki, M., Yamashita, K.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 36296-36303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized MDCK cells.2002

    • Author(s)
      Hara-Kuge, S., Ohkura, T., Ideo H., Shimada, O., Atusmi, S., Yamashita, K.
    • Journal Title

      J. Biol. Chem. 277

      Pages: 16332-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized MDCK cells.2002

    • Author(s)
      Hara-Kuge, S., Ohkura, T., Ideo H., Shimada,O., Atusmi, S., Yamashita, K.
    • Journal Title

      J. Biol. Chem. 277

      Pages: 16332-16339

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] In :, Kameriling, J. P., ed. “Comprehensive Glycoscience". Carbohydrate recognition by cytokines and its relevance to their physiological activities2007

    • Author(s)
      Yamashita, K, Fukushima, K
    • Total Pages
      700
    • Publisher
      Elsevier Pub.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Carbohydrate recognition by cytokines and its relevance to their physiological activities, In :, Kameriling,J.P., ed. "Comprehensive Glycoscience" Amsterdam2007

    • Author(s)
      Yamashita, K., Fukushima, K.
    • Total Pages
      700
    • Publisher
      Elsevier Pub.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Carbohydrate recognition by cytokines and its relevance to their physiological activities.2007

    • Author(s)
      Yamashita, K.
    • Publisher
      Elsvier (In press)
    • Related Report
      2006 Annual Research Report
  • [Book] Carbohydrate recognition by cytokines and its relevance to their physiological activities.2006

    • Author(s)
      Yamashita, K.
    • Publisher
      Elsevier (In press)
    • Related Report
      2005 Annual Research Report
  • [Book] 「糖鎖科学の新展開」サイトカインの生理活性を制御する糖鎖2005

    • Author(s)
      福島 慶子
    • Total Pages
      536
    • Publisher
      エヌ・ティ・エス
    • Related Report
      2005 Annual Research Report
  • [Publications] Fukushima, K: "GPI-anchor recognition of TNF-α modulates apoptosis of U937 cells."Arch.Biochem.Biophys. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Hara-Kuge: "Co-localization of VIP36 and α-amylase via high mannose-type glycan in the rat parotid gland."Glycobiology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seko, A.: "β1,3-N-acetylglucosaminyltransferase-7 (β3Gn-T7) acts efficiently on keratan sulfate-related glycans."FEBS Letters. 556. 216-220 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ono, H: "Novel nonsense mutation (R194X) in the PMM2 gene in a Japanese patient with congenital disorder of glycosylation type Ia."Brain Dev.. 25. 525-528 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada O: "Clusters of VIP-36-positive vesicles between endoplasmic reticulum and golgi apparatus in GH3 cells."Cell Struct Funct.. 28. 155-163 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Seko: "β1,4-Galactosyltrasferase(β4GalT)-IV is specific for GlcNAc 6-O-sulfate."Journal of Biological Chemistry. 278. 9150-9158 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Ideo: "The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity."Glycobiology. 13. 713-723 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Hara-Kuge: "Carbohydrate recognition of vesicular integral protein of 36 kDa (VIP36) in intracellular transport of newly synthesized glycoproteins."Methods in Enzymology. 363. 518-525 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukushima, K: "Carbohydrate recognition of interleuikin-2 in cell proliferation."Methods in Enzymology. 363. 525-532 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukushima, K: "A β-N-acetylglucosaminyl phosphate diester residue is attached to the glycosyl-phosphatidylinositol (GPI) anchor of human placental alkaline phosphatase : a target of the channel-forming toxin aerolysin."Journal of Biological Chemistry. 278. 36296-303 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada O: "Localization of VIP36 in the post-golgi secretory pathway of rat parotid acinar cells."J Histochem Cytochem. 51. 1057-1063 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 福島 慶子: "細胞増殖と糖鎖認識"蛋白質・核酸・酵素. 48. 1120-1125 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada, O.: "Localization of VIP36 in the post-golgi secretory pathway of rat parotid acinar cells"J Histochem Cytochem.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Seko, A.: "β1,4-Galactosyltransferase (β4GalT)-IV is specific for GlcNAc 6-O-Sulfate.278,2003"J Biol Chem.. 278. 9150-9158 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohkura, T.: "Occurrence of secretory glycoprotein-specific GalNAc β1→4GlcNAc sequence in N-glycans in MDCK cells"J Biochem.(Tokyo). 132. 891-901 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara-Kuge, S: "Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized MDCK cells"J Biol Chem.. 277. 16332-16339 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seko, A.: "Ectopical Expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in Colonic Mucinous Adenocarcinoma"Glycobiology. 12. 379-388 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ideo, H.: "High Affinity Binding of Recombinant Human Galectin-4 to SO_3^-→3Galβ1→3GalNAc pyranoside"Glycobiology. 12. 199-208 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seko, A.: "Down-regulation of Gal 3-O-sulfotransferase-2 (Ggal3ST-2) Expression in Human Colonic Non-mucinous Adenocarcinoma"Jpn.J.Cancer Res.. 93. 507-515 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukushima, K: "Methods Enzymol."Academic press (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara-Kuge, S: "Methods Enzymol."Academic press (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 福島慶子: "糖鎖機能-第3の生命鎖-"共立出版(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita, K.: "Handbook of Glycosyltransferases and related genes"Springer社. 652 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 福島慶子: "ポストゲノム時代の糖鎖生物学がわかる"羊土社. 126 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大野耕策: "糖鎖リモデリングマウスと疾病"ニユーサイエンス社. 33 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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