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

• Project/Area Number: 23591430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National 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: ¥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.

Research Products

• [Journal Article] The Integrin-Linked Kinase-PINCH-Parvin Complex Supports Integrin αIIbβ3 Activation (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Agonist stimulation, talin-1, and kindlin-3 are crucial for αIIbβ3 activation in a human megakaryoblastic cell line, CMK (2013)
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [Presentation] Role of ILK-PINCH-parvin complex in supporting functional expression of integrin (2011)
  • 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
• [Presentation] An RNAi screening to identify the molecules involved in integrin αIIbβ3 activation (2011)
  • Author(s): Yasuyuki Matsuda, Shigenori Honda, and Toshiyuki Miyata
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto