Function regulation of proteins and molecular complexes with glycosylation.

• Project/Area Number: 14082101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: FURUKAWA Koichi Nagoya University, 大学院・医学系研究科, 教授 (80211530)
• Co-Investigator(Kenkyū-buntansha): KIMATA Koji Aichi Medical University, Institute fo medicalScience, Professor (10022641) ; KINOSHITA Taro Osaka University, Reserch Institute for Microbial Diseases, Professor (10153165) ; MURAMATSU Takashi Aichi Gakuin University, Faculty of Psychologicaland Physical science, Professor (00030891) ; KNNAGI Reiji Aichi Cancer Center, Molecular Pathology, General Manager (80161389) ; KAWASAKI Toshisuke Ritsumeikan Asia Pacific University, Center of Glyootechnology, Professor (50025706)
• Project Period (FY): 2002 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥113,900,000 (Direct Cost: ¥113,900,000); Fiscal Year 2007: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2006: ¥22,100,000 (Direct Cost: ¥22,100,000); Fiscal Year 2005: ¥22,100,000 (Direct Cost: ¥22,100,000); Fiscal Year 2004: ¥22,100,000 (Direct Cost: ¥22,100,000); Fiscal Year 2003: ¥22,100,000 (Direct Cost: ¥22,100,000); Fiscal Year 2002: ¥22,500,000 (Direct Cost: ¥22,500,000)
• Keywords: glycosylation / glycosyltransferase / glycoprotein / glycolinid / proteoglycan / signal / Knolout / bioreyulation / ノックアウト / グライコミクス / 分子複合体 / ミクロドメイン / 機能調節

Research Abstract

平成14〜18年度の特定領域研究「糖鎖によるタンパク質と分子複合体の機能調節」の研究成果のとりまとめのために、主に2つの事業を実施した。
1つ目に、11月26日、27日に東京品川において公開シンポジウムを開催し、著明な成果を上げた班員を中心に研究発表を行った。実際には、日本糖鎖科学コンソーシアム第5回シンポジウムの中で本領域のセッションを設け、合計6名の講演者による発表を行い、活発な討論を行った。
6名の講演内容は岡昌吾(京都大学医学部保健学科)「神経可塑性とHNK-1糖鎖」、桝和子(筑波大学大学院)「新規のエンドスルファターゼSulfFPによるヘパラン硫酸糖鎖修飾の生理機能の解明」、北爪 しのぶ(理化学研究所)「シアル酸転移酵素の切断・分泌機構-生理的意義の解明と肝疾患マーカーとしての応用」、永井尚子(愛知医科大学 分子医化学研究所)「ヘパラン硫酸60-硫酸基転移酵素HS6ST3の細胞内局在調節機構、木下タロウ(大阪大学 微生物病研究所)「「GPIアンカー生合成酵素の欠損と疾患」、門松健治(名古屋大学大学院 生化学第一講座)神経損傷とケラタン硫酸」。
2つ目には、計画班員、公募班員の研究成果をまとめ、成果報告書を作製して班員、班友および領域の内外の研究者、省庁等に配付した。内容としては各班員による研究のまとめと共に特許申請、テレビや新聞などの取材、発表論文、主な論文のreprint等をとりまとめた。
さらに、10月17日には最終ヒヤリングを行い、全体のまとめの報告書を提出すると共に、プレゼンテーションを行い、審査委員との質疑応答を行った。A評価をいただいた。
また、審査委員会のコメントとして、本研究の内容の進展を評価すると共に、成果の応用的研究を発展させるべく、助言をいただいた。

Research Products

• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in overt-expression of 9-O-acetyl GD3 irrespective of Tis21. (2008)
  • Author(s): Furukawa, K., et. al.
  • Journal Title: J. Neurochem. (In press)
  • Peer Reviewed
• [Journal Article] Cloning and characterization of anovel phosphomannan-binding lectin from porcine serum. (2007)
  • Author(s): Ma BY, Nakamura N., et. al.
  • Journal Title: J Biol Chem. 282(17) Pages: 12963-12975
  • Peer Reviewed
• [Journal Article] Essentioal role of heparan sulfate 2-O-sulfotransferase in chick limb bud patterning and development. (2007)
  • Author(s): Kobayashi T., et. al.
  • Journal Title: J Biol Chem. 2007Jul 6 Pages: 19589-97
  • Peer Reviewed
• [Journal Article] Mice deficient in heparan sulfate 6-0-sulfotransferase-1 exhibit defective heparin sulfate biosynthesis, abnormal placentation, and late embryonic lethality. (2007)
  • Author(s): Habuchi H,., et al
  • Journal Title: J Biol Chem. 282 Pages: 15578-15588
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Biosynthesis of Glycolipids. In Comprehensive Glycoscience. Article (2007)
  • Author(s): Furukawa K,., et al
  • Journal Title: Elsevier, Oxford, UK No. : 00037
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the biosynthesis of the HNK-1 carbohydrate epitope. (2006)
  • Author(s): Shiba T,., et al
  • Journal Title: Protein 65 Pages: 499-508
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mice deficient in heparan sulfate 6-0-sulfotransferase-1 exhibit defective heparan sulfate biosynthesis, abnormal placentation, and late embryonic lethality. (2006)
  • Author(s): Habuchi H,., et al
  • Journal Title: J Biol Chem. 282 Pages: 15578-15588
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers (2006)
  • Author(s): Ko, K, et al.
  • Journal Title: Oncogene 25 Pages: 6924-6935
• [Journal Article] Versican/PG-M regulates chondrogenesis as an extracellular matrix molecule crucial for mesenchymal condensation (2006)
  • Author(s): Kamiya N, et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 2390-2400
• [Journal Article] Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). (2006)
  • Author(s): Inoue N, et al.
  • Journal Title: Blood 108 Pages: 4232-4236
• [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors (2006)
  • Author(s): Muramatsu H, et al.
  • Journal Title: Genes Cells 11 Pages: 1405-1417
• [Journal Article] Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells (2006)
  • Author(s): Yin J, et al.
  • Journal Title: Cancer Res. 66 Pages: 2937-2945
• [Journal Article] Physical and functional association of glucuronyltransferases and sulfotransferase involved in HNK-1 biosynthesis (2006)
  • Author(s): Kizuka Y, et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 13644-13651
• [Journal Article] Taegeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to veritoxins (2006)
  • Author(s): Okuda T, Tokuda N, Numata S, Furukawa K, et al.
  • Journal Title: J. Biol. Chem. (in press)
• [Journal Article] Molecular cloning and characterization of chick spacrcan (2006)
  • Author(s): Inoue Y, Yoneda M, Zhao J, Kimata K, et al.
  • Journal Title: J. Biol. Chem. (in press)
• [Journal Article] Ganglioside GD3 promotes cell growth and invasion through pl30Cas and paxillin in malignant melanoma cells. (2005)
  • Author(s): Hamamura K,., et al
  • Journal Title: Proc Natl Acad Sci USA 102 Pages: 11041-11046
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ganglioside GD3 promotes cell growth and innasion through p130 Cas and paxillin in malignant melanoma cells (2005)
  • Author(s): Hmamura, K., et al
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 11041-11046
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells (2005)
  • Author(s): Hamamura K, Furukawa K, Hayashi T, Furukawa K, et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA, 102 Pages: 11041-11046
• [Journal Article] RNA polymerase II is required for siRNA generation and peri-centromeric heterochromatin formation in fission yeast (2005)
  • Author(s): Kato H, Goto DB, Martienssen RA, Urano T, Furukawa K, et al.
  • Journal Title: Science 309 Pages: 467-469
• [Journal Article] A non-sulfated form of the HNK-1 carbohydrate is expressed in mouse kidney (2005)
  • Author(s): Tagawa H, Kizuka Y, Ikeda T, Itoh S, Kawasaki T, et al.
  • Journal Title: J. Biol. Chem., 280 Pages: 23876-23883
• [Journal Article] N-Acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules (2005)
  • Author(s): Kawashima H, Petryniak B, K, Kadomatsu K, Muramatsu T, et al.
  • Journal Title: Nat. Immunol. 6 Pages: 1096-1104
• [Journal Article] Over-expressed GM1 suppresses NGF signals by modulating the intracellular localization of NGF receptors and membrane fluidity in PC12 cells. (2004)
  • Author(s): Furukawa, K. et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 33368-33378
• [Journal Article] Carbohydrate Mimicry between Human Ganglioside GM1 and Campylobacter jejuni Lipo-oligosaccharide Causes Guillain-Barre Syndrome. (2004)
  • Author(s): Furukawa, K. et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 101 Pages: 11404-11409
• [Journal Article] Glycosphingolipids in engineered mice. (2004)
  • Author(s): Furukawa, K. et al.
  • Journal Title: Semin.Cell Dev.Biol. 15 Pages: 389-396
• [Journal Article] 糖鎖科学の新局面 実験医学 特集 糖鎖シグナルによる多彩な生体機能制御 シグナル伝達、細胞分裂、神経ネットワーク形成制御から疾患まで (2004)
  • Author(s): 古川 鋼一
  • Journal Title: 実験医学 22 Pages: 912-915
• [Journal Article] Purification and characterization of two recombinant human glucuronyltransferases involved in the biosynthesis of HNK-1 carbohydrate in Escherichia coli. (2004)
  • Author(s): Kawasaki, T. et al.
  • Journal Title: Protein Expr.Purif. 35 Pages: 111-119
• [Journal Article] Selective expression and functional characteristics of three mammalian hyaluronan synthases in oncogenic malignant transformation. (2004)
  • Author(s): Kimata, K. et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 18679-18687
  • NAID: 110003994219
• [Presentation] Molecular complex formation based on glycoshingolipids as a functional plet from to support cancer cells (2007)
  • Author(s): Koichi Furukawa
  • Organizer: 第80回日本生化学学会大会、第30回日本分子生物学会年会の合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-15
• [Presentation] Molecular complex formation based on glycosphingolipids as a functional platform to support cancer cells (2007)
  • Author(s): Koichi Furukawa
  • Organizer: 第80回日本生化学学会大会、第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Molecular complex formation based on Glycoshiyslipids as a functional platform to support cancer cells. (2007)
  • Author(s): Koichi Furukawa., et al
  • Organizer: Compined Annnal Meeting of Japanse Societies of Biochemistry and Molecular Biology.
  • Place of Presentation: Yokohama
  • Year and Date: 2007-12-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Knockout mice and glycolipids. In Comprehensive Glycoscience. Article No, :00086 pp149-157 (2007)
  • Author(s): Furukawa, K., et. al.
  • Total Pages: 800
  • Publisher: Elsevier Ltd
• [Book] Biosynthesis of Glycolipids. In Comprehensive Glycoscience. Article No. : 00037, pp1O5-114 (2007)
  • Author(s): Furukawa K,., et al
  • Total Pages: 800
  • Publisher: Elsevier, Oxford, UK
  • Description: 「研究成果報告書概要(和文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.glycomics.ne.jp/
• [Patent(Industrial Property Rights)] ヘパラン硫酸6-O-硫酸基転移酵素 (2006)
  • Inventor(s): 羽渕 弘子, 他
  • Industrial Property Rights Holder: 生化学工業株式会社
  • Acquisition Date: 2006-06-23
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Chen, H.H.et al.: "Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene."Int.J.Cancer. 103. 169-176 (2003)
• [Publications] Furukawa, K., Horie, M., Okutomi, K., Sugano, S., Furukawa.K.: "Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene."Biochim.Biophys.Acta.. 1627. 71-78 (2003)
• [Publications] Tsuchida, A.et al.: "Synthesis of disialyl Lewis a structure in colon cancer cell lines by a sialyltransferase ST6GalNAc VI responsible for the syntheis of α -series gangliosides."J.Biol.Chem.. 278. 22787-22794 (2003)
• [Publications] Iwamura, K. et al.: "The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene : A solution of the P1/P2/p puzzle."J.Biol.Chem.. 278. 44429-44438 (2003)
• [Publications] Yada, T.et al.: "Chondroitin sulfate synthase-3. Molecular cloning and characterization."J.Biol.Chem.. 278. 39711-39725 (2003)
• [Publications] Kakuda, S.et al.: "Structural basis for acceptor substrate recognition of a human glucuronyltransferase, GlcAT-P, an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1."J.Biol.Chem.. (In press). (2004)
• [Publications] Mitsuda, T. et al.: "Over-expression of ganglioside GM1 results in the dispersion of platelet derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals"J.Biol.Chem.. 277. 11239-11246 (2002)
• [Publications] Inoue, M. et al.: "Refractory skin injury in the complex knock-out mice expressing only GM3 ganglioside"J.Biol.Chem.. 277. 29881-29888 (2002)
• [Publications] Nakamura, Y. et al.: "Identification of a Drosophila gene encoding xylosylprotein b4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis"J.Biol.Chem.. 277. 46280-46288 (2002)
• [Publications] Itano, N. et al.: "Abnormal accumulation of hyaluronan matrix diminishes contact inhibition of cell growth and promotes cell migration"Proc.Natl.Acad.Sci. USA. 99. 3609-3614 (2002)
• [Publications] Shibata, Y. et al.: "Nuclear targeting by the growth factor midkine"Mol.Cell.Biol.. 22. 6788-6796 (2002)
• [Publications] Ohishi, K., Nagamune, K., Maeda, Y., Kinoshita, T.: "Two subunits of GPI transamidase GPI8 and PIG-T form a functionally important intermolecular disulfide bridge"J.Biol.Chem.. (in press). (2003)