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Studies on the structure and function of new vascular endothelial growth factors

Research Project

Project/Area Number 18370048
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

MORITA Takashi  Meiji Pharmaceutical University, 薬学部, 教授 (90128108)

Co-Investigator(Kenkyū-buntansha) YAMAZAKI Yasuo  明治薬科大学, 薬学部, 助教 (30308621)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥17,920,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2008: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywords血管内皮増殖因子 / VEGF / 血管透過性 / 生体生命情報学 / 分子認識 / 蛋白質 / ゲノム / 生体分子
Research Abstract

申請者は、VEGFの分子作用機序の解明を目標に、ヘビ毒腺に発現する毒型VEGF (VEGF-F) に焦点を当て、生化学的および生物学的な解析を行った。その結果、毒ヘビに発現する毒型VEGFは機能的に重要な領域の構造 (受容体結合ループおよびC末端領域) を多様化させることで、その機能を多様化していることを明らかにした。次に、vamminをはじめとする異なるリガンド特性を持つVEGFを用いた超微形態学的解析より、VEGFの血管透過性の亢進に伴う血管壁の超微構造変化 (VVOおよびfenestrae形成) は、リガンドの受容体選択性によって異なることを示した。さらに、種々のヘビ毒よりVEGFとは異なる新しいVEGF受容体結合タンパク質、KDR-bp (Lys49-PLA2) を同定した。VEGFの血管透過性亢進作用は癌性浮腫や腹水、炎症細胞・癌細胞浸潤の原因となることから、本研究の成果は、それら病態機序の解明および分子治療に貢献することと期待している。さらに、KDR-bpの発見はKDRの新たな機能探索ならびにVEGFおよびVEGF受容体分子標的物質の開発研究において有用なツールとなると考える。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (44 results)

All 2009 2008 2007 2006 Other

All Journal Article (22 results) (of which Peer Reviewed: 17 results) Presentation (18 results) Book (4 results)

  • [Journal Article] VEGF-A and VEGF-F evoke distinct changes in vascular ultrastructure.2009

    • Author(s)
      Matsunaga Y, Yamazaki Y, Suzuki H, Morita T
    • Journal Title

      Biochem. Biophys. Res. Commun. 379

      Pages: 872-875

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] VEGF-A and VEGF-F evoke distinct changes in vascular ultrastructure.2009

    • Author(s)
      Matsunaga Y
    • Journal Title

      Biochem. Biophys. Res. Commun. 379

      Pages: 872-875

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Snake venom vascular endothelial growth factors (VEGF-Fs) exclusively vary their structures and functions among species.2009

    • Author(s)
      Yamazaki Y
    • Journal Title

      J. Biol. Chem. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytically inactive phospholipase A2 homologue binds to vcascular endothelial growth factor receptor-2 via a C-terminal loop region.2008

    • Author(s)
      Fujisawa D, Yamazaki Y, Lomonte B, Morita T
    • Journal Title

      Biochem. J. 411

      Pages: 515-522

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus serotype 5 hexon mediates liver gene transter.2008

    • Author(s)
      Waddington SN, McVey JH, Bhella D, Parker AL, Barker K, Atoda H, Pink R, Buckley SMK, Greig JA, Denby L, Custers J, Morita T, Francischetti IMB, Monteiro RQ, Barouch DH, Rooijen NV, Napoli C, Havenga MJE, Nicklin SA, Baker AH
    • Journal Title

      Cell 132

      Pages: 397-409

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus serotype 5 hexon mediates liver gene transter.2008

    • Author(s)
      Waddington SN
    • Journal Title

      Cell 132

      Pages: 397-409

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytically inactive phospholipase A_2 homologue binds to vcascular endothelial growth factor receptor-2 via a C-teminal loop region.2008

    • Author(s)
      Fujisawa D
    • Journal Title

      Biochem.J. 411

      Pages: 515-522

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of vascular permeability of VEGF is enhanced by KDR-binding proteins.2007

    • Author(s)
      Yamazaki Y, Nakano Y, Imamura T, Morita T
    • Journal Title

      Biochem. Biophys. Res. Commun. 355

      Pages: 693-699

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of vascular permeability of VEGF is enhanced by KDR-binding proteins.2007

    • Author(s)
      Yamazaki Y
    • Journal Title

      Biochem.Biophys.Res.Commun1 355

      Pages: 693-699

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-and gender-related differences of plasma prothrombin activity levels.2007

    • Author(s)
      Sakata T
    • Journal Title

      Thromb.Haemost 97

      Pages: 1052-1053

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Snake venom components affecting blood coagulation and the vascular system:Structural similarities and marked diversity2007

    • Author(s)
      Yamazaki Y
    • Journal Title

      Current Pharmaceutical Design 13

      Pages: 2872-2886

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管内皮増殖因子ファミリー-その多様な構造と機能-2007

    • Author(s)
      山崎 泰男
    • Journal Title

      日本血栓止血学会誌 18

      Pages: 3-15

    • NAID

      10026114149

    • Related Report
      2007 Annual Research Report
  • [Journal Article] PIVKA-IIの生化学2007

    • Author(s)
      森田 隆司
    • Journal Title

      肝胆膵 54

      Pages: 459-463

    • Related Report
      2007 Annual Research Report
  • [Journal Article] The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2 in cultured human brain microvascular endothelial cells.2006

    • Author(s)
      Kaji T, Yamamoto C, Oh-i M, Fujiwara Y, Yamazaki Y, Morita T, Plaas AH, Wight TN
    • Journal Title

      Biochim. Biophys. Acta. 1760

      Pages: 1465-1474

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Localization of heparin- and neuropilin-1-recognition sites of viral VEGFs.2006

    • Author(s)
      Tokunaga Y, Yamazaki Y, Morita T
    • Journal Title

      Biochem. Biophys. Res. Commun. 348

      Pages: 957-962

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of a monoclonal antibody B1 that recognizes phosphorylated Ser-158 in the activation peptide region of human coagulation factor IX.2006

    • Author(s)
      Atoda H, Yokota E, Morita T
    • Journal Title

      J. Biol. Chem. 281

      Pages: 9314-9320

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2.2006

    • Author(s)
      Suzuki-Inoue K, Fuller GLJ, Garcia A, Eble JA, Pohlmann S, Inoue O, Gartner TK, Hughan SC, Pearce AC, Laing GD, Theakston RD, Schweighoffer E, Zitzmann N, Morita T, Tybulewicz VLJ, Ozaki Y, Watson SP
    • Journal Title

      Blood 107

      Pages: 542-549

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Different contributions of polymorphism in VKORC1 and CYP2C9 to intra- and inter- population differences in maintenance dose of warfarin in Japanese, Caucasians and African- Americans.2006

    • Author(s)
      Takahashi H, Wilkinson GR, Nutescu EA, Morita T, Ritchie MD, Scordo MG, Pengo V, Barban M, Padrini R, Ieiri I, Otsubo K, Kashima T, Kimura S, Kijima S, Echizen H
    • Journal Title

      Pharmacogenetics Genomics 16

      Pages: 101-110

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of a monoclonal antibody B1 that recognizes phosphorylated Ser-158 in the activation peptide region of human coagulation factor IX.2006

    • Author(s)
      阿刀田 英子ら
    • Journal Title

      J. Biol. Chem. 281(14)

      Pages: 9314-9320

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Localization of heparin- and neuropilin-1-recognition sites of viral VEGFs.2006

    • Author(s)
      徳永 優子ら
    • Journal Title

      Biochem. Biophys. Res. Commun. 348

      Pages: 957-962

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2 in cultured human brain microvascular endothelial cells.2006

    • Author(s)
      鍛冶 利幸ら
    • Journal Title

      Biochem. Biophys. Acta. 1760

      Pages: 1465-1474

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Snake venom vascular endothelial growth factors (VEGF-Fs) exclusively vary their structures and functions among species.

    • Author(s)
      Yamazaki Y, Matsunaga Y, Tokunaga Y, Obayashi S, Saito M and Morita T
    • Journal Title

      J. Biol. Chem. in press

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 血液凝固IX因子と抗凝固タンパク質(IX/X-bpおよびIX-bp)の相互作用に対するMg^<2+>の影響2008

    • Author(s)
      石川みどり、山崎泰男、森田隆司
    • Organizer
      第55回毒素シンポジウム
    • Place of Presentation
      山梨
    • Related Report
      2008 Final Research Report
  • [Presentation] 組織型および毒型VEGF(血管内皮増殖因子)のゲノム構造解析2008

    • Author(s)
      山崎泰男、齋藤麻衣、徳永優子、森田隆司
    • Organizer
      第55回毒素シンポジウム
    • Place of Presentation
      山梨
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 血液凝固IX因子と抗凝固タンパク質(IX/X-bpおよびIX-bp)の相互作用の速度論的解析2008

    • Author(s)
      石川みどり、山崎泰男、森田隆司
    • Organizer
      日本薬学会128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 異なるC末端ドメインを持つVEGFキメラの創製とその生物活性2008

    • Author(s)
      夘月博和、山崎泰男、森田隆司
    • Organizer
      日本薬学会128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 組織型と毒型の血管内皮増殖因子のゲノム構造解析とその進化論的考察2008

    • Author(s)
      齋藤麻衣、徳永優子、長谷川芳裕、山崎泰男、森田隆司
    • Organizer
      日本薬学会128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 血液・血管研究の新しい視点-毒タンパク質研究から何がわかるのか?-2007

    • Author(s)
      山崎 泰男
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2008)、ワークショップ「ベノミクス:毒生物ゲノムプロジェクト」
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] ハブ由来の組織型および毒型VEGF(血管内皮増殖因子)のゲノム構造解析2007

    • Author(s)
      齋藤 麻衣
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] ニューロピリン-1およびヘパリン結合性の異なる血管内皮増殖因子組換え体の調製2007

    • Author(s)
      夘月 博和
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] 抗凝固活性を有すると報告された_L-アミノ酸参加酵素の抗凝固メカニズムの解析2007

    • Author(s)
      藤澤 大輔
    • Organizer
      第30回日本血栓止血学会学術集会
    • Place of Presentation
      三重
    • Year and Date
      2007-11-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] Inactive Phospholipase A_2 Homologue Binds to VEGF Receptor-2 Via Its C-Terminal Loop Regon2007

    • Author(s)
      Fuisawa D
    • Organizer
      The lst Seminar on Bioactive Natural Products from Marine Organisms/EndophyticFungi amd The JSPS 2nd Medicinal Chemistry Seminar of Asia/Africa Science Platform Program
    • Place of Presentation
      Phuket,Thailand
    • Year and Date
      2007-10-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] Use of Snake Venom Proteins in Studies of the Structure and Function of Coagulation Factors2007

    • Author(s)
      Morita T
    • Organizer
      The Ist Seminar on Bioactive Natural Products from Marine Organisms/EndophyticFungi and The JSPS 2nd Medicinal ChemistrySeminar of Asia/Africa Science Platform Program
    • Place of Presentation
      Phuket,Thailand
    • Year and Date
      2007-10-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Trimeresurus flavoviridis毒腺cDNAライブラリーの網羅的解析2007

    • Author(s)
      長谷川 芳裕
    • Organizer
      第54回毒素シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2007-09-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Echis pyramidum毒由来の非ヘパリン結合性VEGFの単離とその性質2007

    • Author(s)
      乙部 清香
    • Organizer
      第54回毒素シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2007-09-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] ヘビ毒には多様な構造と性質をもつVEGFが含まれている2007

    • Author(s)
      松永 幸子
    • Organizer
      第54回毒素シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2007-09-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Augmentation of Vascular Permeability of Vascular Endothelial Growth Factor(VEGF)is Enhanced by VEGF Recetor 2-bindingProteins2007

    • Author(s)
      Yamazaki Y
    • Organizer
      XXIst Congress of the International Society on Thrombosis and Haemostasis, 53rd Annual SSC Meeting
    • Place of Presentation
      Geneva,Switzerland
    • Year and Date
      2007-07-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular and Functional Diversity of Snake Venom VEGFS2007

    • Author(s)
      Matsunaga Y
    • Organizer
      XXIstCongress of the International Society on Thrombosis and Haemostasis, 53rd Annual SSC Meeting
    • Place of Presentation
      Geneva,Switzerland
    • Year and Date
      2007-07-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] Identification of VEGF Receptor-binding Sites of KDR-binding Protein2007

    • Author(s)
      Fujisawa D
    • Organizer
      XXIst Congress of the International Society on Thrombosis and Haemostasis, 53rd Annual SSC Meeting
    • Place of Presentation
      Geneva,Switzerland
    • Year and Date
      2007-07-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] KDR結合タンパク質はVEGFの血管透過性元進作用を増強する2007

    • Author(s)
      山崎 泰男
    • Organizer
      第8回Phamlaco-Hematologyシンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2007-06-08
    • Related Report
      2007 Annual Research Report
  • [Book] Snake Venoms and Other Toxic Components Affecting Thrombosis and Hemostasis. In: Recent Advances in Thrombosis and Hemostasis 2008. (Tanaka K, Davie EW eds)2008

    • Author(s)
      Yamazaki Y, Morita T
    • Publisher
      Springer
    • Related Report
      2008 Final Research Report
  • [Book] Recent Advances in Thrombosis and Hemostasis 20082008

    • Author(s)
      Yamazaki Y
    • Publisher
      Snake Venoms and Other Toxic Components Affecting Thrombosis and Hemostasis
    • Related Report
      2008 Annual Research Report
  • [Book] Xa阻害薬のすべて2007

    • Author(s)
      山崎 泰男
    • Publisher
      株式会社先端医学社
    • Related Report
      2007 Annual Research Report
  • [Book] Molecular and functional diversity of vascular endothelial growth factors2006

    • Author(s)
      Yamazaki Y, Morita T
    • Publisher
      Mol. Divers.
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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