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Elucidation of the role of ILK in the functional expression of beta3 integrins and investigation of the ILK-related molecules

Research Project

Project/Area Number 23591430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

HONDA Shigenori  独立行政法人国立循環器病研究センター, 研究所, 室長 (00303959)

Co-Investigator(Renkei-kenkyūsha) TOMIYAMA Yoshiaki  大阪大学, 医学研究科, 准教授 (80252667)
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsインテグリン / β3インテグリン / ILK / β3インテグリン
Outline of Final Research Achievements

β3 integrins are members of the integrin family consisted of αIIbβ3 and αVβ3. αIIbβ3, a major integrin expressed on platelets, is critical for platelet aggregation mediated by bindings of fibrinogen and von Willebrand factor. αVβ3 (vitronectin receptor), an integrin widely expressed on several cell types including blood vessel tissue constitutive cells and tumor cells, play important roles in diverse vascular disease states, tumor proliferation and metastasis.
Integrin-linked kinase (ILK) is an important signaling regulator that assembles into the heteroternary complex with adaptor proteins PINCH and parvin (termed the IPP complex). We recently reported that ILK is important for integrin activation in a Chinese hamster ovary (CHO) cell system. In this study, we further investigated the underlying mechanisms for ILK-dependent integrin activation, and we found that the IPP complex rather than ILK alone plays an important role and supports αIIbβ3 activation.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 2012 2011

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (6 results)

  • [Journal Article] The Integrin-Linked Kinase-PINCH-Parvin Complex Supports Integrin αIIbβ3 Activation2013

    • Author(s)
      Hond S, Shirotani-Ikejima H, Tadokoro S, Tomiyama Y, Miyata T
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 12 Pages: 1-13

    • DOI

      10.1371/journal.pone.0085498

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Agonist stimulation, talin-1, and kindlin-3 are crucial for αIIbβ3 activation in a human megakaryoblastic cell line, CMK2013

    • Author(s)
      Nakazawa T, Tadokoro S, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y.
    • Journal Title

      Exp Hematol.

      Volume: 41(1) Issue: 1 Pages: 79-90

    • DOI

      10.1016/j.exphem.2012.09.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recognition of highly restricted regions in the β-propeller domain of αIIb by platelet-associated anti-αIIbβ3 autoantibodies in primary immune thrombocytopenia.2012

    • Author(s)
      Kiyomizu K, Kashiwagi H, Nakazawa T, Tadokoro S, Honda S, Kanakura Y, Tomiyama Y.
    • Journal Title

      Blood

      Volume: 120(7) Issue: 7 Pages: 1499-1509

    • DOI

      10.1182/blood-2012-02-409995

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] インテグリンαIIbβ3機能発現におけるIntegrin-linked kinaseの役割2014

    • Author(s)
      本田繁則, 池島裕子, 田所誠司, 冨山佳昭, 宮田敏行
    • Organizer
      日本血栓止血学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-29 – 2014-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] インテグリンαIIbβ3活性化変異, αIIb (R990W) ノックインマウスの解析2014

    • Author(s)
      清水一亘, 柏木浩和, 森川陽一郎, 加藤 恒, 田所誠司, 坂野史明, 小亀浩市, 本田繁則, 金倉 譲, 宮田敏行, 冨山佳昭
    • Organizer
      日本血栓止血学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-29 – 2014-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Primary ITP患者の血小板関連抗αIIbβ3抗体のエピトープに関する検討2013

    • Author(s)
      清水一亘,柏木浩和,加藤 恒,田所誠司,本田繁則,金倉 譲,冨山佳昭
    • Organizer
      日本血栓止血学会学術集会
    • Place of Presentation
      山形県
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト巨核球株CMKにおけるαIIbβ3の活性化にはagonist, talin-1, kindlin-3が必須である2012

    • Author(s)
      中澤剛士、田所誠司、清水一亘、柏木浩一、本田繁則、金倉 譲、冨山佳昭
    • Organizer
      日本血栓止血学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of ILK-PINCH-parvin complex in supporting functional expression of integrin2011

    • Author(s)
      Shigenori Honda, Hiroko Shirotani-Ikejima, Yasuyuki Matsuda, Seiji Tadokoro, Yoshiaki Tomiyama, and Toshiyuki Miyata
    • Organizer
      XXIII Congress of The International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Research-status Report
  • [Presentation] An RNAi screening to identify the molecules involved in integrin αIIbβ3 activation2011

    • Author(s)
      Yasuyuki Matsuda, Shigenori Honda, and Toshiyuki Miyata
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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