• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

運動する細胞の先端に形成される浸潤装置複合体の構造と機能

Research Project

Project/Area Number 18054022
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

村井 稔幸  Osaka University, 医学系研究科, 助教 (20311756)

Co-Investigator(Kenkyū-buntansha) 池上 貴久  大阪大学, 蛋白質研究所, 准教授 (20283939)
保坂 晴美  大阪大学, 蛋白質研究所, 特任研究員 (70423134)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2007: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywords蛋白質 / 酵素 / 癌
Research Abstract

細胞運動は、癌細胞の浸潤や免疫系細胞の炎症部位への浸潤などにおいて重要である。われわれは、細胞接着レセプターCD44が、浸潤性細胞の運動先端部に集積し、膜型メタロプロテアーゼにより切断を受けること、そして、その現象が、細胞運動の駆動力を発生させることを見出した。本研究課題は、これらの独自の研究成果に基づき、浸潤装置複合体の構造と機能を明らかにすることにより、細胞運動・浸潤のメカニズムを解明することを目指した。そして、次の点について、細胞の運動先端部位に形成される浸潤装置複合体の構造と機能の解明を進めた。機能面では、臨床的に癌組織で顕著に検出される接着レセプターCD44のリガンドであるピアルロン酸の低分子量化が、浸潤性癌細胞が産生するピアルロン酸分解酵素・ヒアルロニダーゼの作用によりオートクリン様の機序で起こっており、それが浸潤装置複合体の構成を変化させることにより、細胞運動性を亢進することを明らかにした。また、癌細胞に多く発現する上皮成長因子受容体からのシグナルによっても、CD44の機能による癌細胞の運動性が亢進し、そのときに浸潤装置複合体がダイナミックに作動していることを明らかにした。構造面では、浸潤装置構成分子の大量発現、および、高純度精製を進め、溶液NMRなどによる構造解析を行い、フレキシブルに動く構造を有することを見出した。以上、CD44を中心とした細胞運動・浸潤の重要な機能調節機構が明らかとなった。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006

All Journal Article (15 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Crystal structure of bovine lipoyltransferase in complex with lipoyl-AMP.2007

    • Author(s)
      Fujiwara, K., et. al.
    • Journal Title

      Journal of Molecular Biology 371

      Pages: 222-234

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cores and pH-dependent dynamics of ferredoxin-NADP^+ reductase revealed by hydrogen/deuterium exchange.2007

    • Author(s)
      Lee, Y.H., et. al.
    • Journal Title

      The Journal of Biological Chemistry 282

      Pages: 5959-5967

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular interaction of ferredoxin and ferredoxin-NADP^+ reductase from human malaria parasite.2007

    • Author(s)
      Kimata-Ariga, Y., et. al.
    • Journal Title

      Journal of Biochemistry 142

      Pages: 715-720

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10.2006

    • Author(s)
      Murai, T. et al.
    • Journal Title

      Biochemical Journal 395・1

      Pages: 65-71

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Targeting AMAP1 and cortactin binding bearing an atypical SH3/proline interface for prevention of breast cancer invasion and metastasis.2006

    • Author(s)
      Hashimoto, S. et al.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 103・18

      Pages: 7036-7041

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel way to express proline-selectively labeled proteins with a wheat germ cell-free protein synthesis system.2006

    • Author(s)
      Shimizu, M. et al.
    • Journal Title

      Journal of Biochemistry 140・3

      Pages: 453-456

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ^1H, ^<13>C and ^<15>N resonance assignments of the pyrazinamidase from Mycobacterium tuberculosis.2006

    • Author(s)
      Son, W.S.et al.
    • Journal Title

      Journal of Biomolecular NMR 36

      Pages: 60-60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structure of the cadherin-related neuronal receptor/protocadherin-alpha first extracellular cadherin domain reveals diversity across cadherin families.2006

    • Author(s)
      Morishita, H. et al.
    • Journal Title

      The Journal of Biological Chemistry 281・44

      Pages: 33650-33663

    • Related Report
      2006 Annual Research Report
  • [Journal Article] NMR assignment of the chitin-binding domain of a hyperthermophilic chitinase from Pyrococcus furiosus.2006

    • Author(s)
      Mine, S. et al.
    • Journal Title

      Journal of Biomolecular NMR 36

      Pages: 70-70

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of thermal treatments on the recovery of adsorbed water and photocatalytic activities of TiO_2 photocatalytic systems.2006

    • Author(s)
      Nosaka, A.Y. et al.
    • Journal Title

      Journal of Physical Chemistry B 110・16

      Pages: 8380-8385

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A new solution structure of ATP synthase subunit c from thermophilic Bacillus PS3, suggesting a local conformational change for H^+-translocation.2006

    • Author(s)
      Nakano, T. et al.
    • Journal Title

      Journal of Molecular Biology 358・1

      Pages: 132-144

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Specific binding of CO to tetraheme cytochrome c_3.2006

    • Author(s)
      Takayama, Y. et al.
    • Journal Title

      Biochemistry 45・10

      Pages: 3163-3169

    • Related Report
      2006 Annual Research Report
  • [Journal Article] NMR study of the electron transfer complex of plant ferredoxin and sulfite reductase : Mapping the interaction sites of ferredoxin.2006

    • Author(s)
      Saitoh, T. et al.
    • Journal Title

      The Journal of Biological Chemistry 281・15

      Pages: 10482-10488

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of the substrate interaction region of the chitin-binding domain of Streptomyces griseus chitinase C.2006

    • Author(s)
      Akagi, K. et al.
    • Journal Title

      Journal of Biochemistry 139・3

      Pages: 483-493

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic N-terminal region, revealing the structural basis of specific recognition by the orexin-1 receptor.2006

    • Author(s)
      Takai, T. et al.
    • Journal Title

      Journal of Peptide Science 12・7

      Pages: 443-454

    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi