Cloning and analysis of molecules involved in functional regulation of β3 integrin

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: HONDA Shigenori National Cardiovascular Center Research Institute, 分子病態部, 室長 (00303959)
• Co-Investigator(Kenkyū-buntansha): TOMIYAMA Yoshiaki 大阪大学, 医学部附属病院, 教授 (80252667)
• Project Period (FY): 2008 – 2010
• Keywords: β3インテグリン / シグナル伝達 / ILK / クローニング

Research Abstract

(1) We clarified that ILK is important for functional expression of β3 integrin and this process is necessary for the full-length of ILK but not each ILK-domain fragment. It was suggested that the kinase activity of ILK is not essential for integrin activation. In addition, we showed that ILK forms a complex with an intracellular adaptor protein, PINCH and Parvin, and this complex formation might be needed to stabilize each protein.
(2)We established mutant cell lines with inactivated integrin αIIbα6Bβ3 to which is converted by a treatment of chemical mutagen. Transfection of ILK cDNA into the mutant cells did not induce integrin activation, suggesting that those mutant cells might have defects in molecules except for ILK, which resulted in the inactivated integrin state. We are performing expression cloning to isolate molecules involved in functional expression of β3 integrin.

Research Products

• [Journal Article] Biochem Biophys (2010)
  • Author(s): T.Ohmori, Y.Kashiwakura, A.Ishiwata, S.Madoiwa, J.Mimuro, S.Honda, T.Miyata, Y.Sakata.
  • Journal Title: Res Commun 400 Pages: 323-328
• [Journal Article] 「キンドリンとインテグリン活性化」Annual Review 血液2010(高久史麿・小澤敬也・坂田洋一・金倉譲・小島勢二編集) (2010)
  • Author(s): 冨山佳昭、本田繁則
  • Journal Title: 中外医学社 Pages: 160-167
• [Journal Article] Integrin-linked kinase associated with integrin activation. (2009)
  • Author(s): S.Honda, Shirotani-Ikejima H, S.Tadokoro, Y.Maeda, T.Kinoshita, Y.Tomiyama, T.Miyata
  • Journal Title: Blood 113 Pages: 5304-5313
• [Journal Article] Blood Coagul (2009)
  • Author(s): J.Ishikawa, H.Okada, H.Kato, S.Takeshita, S.Honda, T.Kawasaki, E.Suehisa, H.Tsuji, S.Madoiwa, Y.Sakata, T.Kojima, M.Murata, Y.Ikeda, Y.Kokubo, T.Okamura, H.Tomoike, T.Miyata
  • Journal Title: Fibrinolysis 20 Pages: 22-26
• [Journal Article] 変異導入法を用いた血小板インテグリンαIIbβ3の機能調節に関わる分子の探索 (2009)
  • Author(s): 本田繁則、池島-城谷裕子、松田泰幸、田所誠司、前田祐輔、木下タロウ、冨山佳昭、宮田敏行
  • Journal Title: 日本血栓止血学会誌 20(6) Pages: 615-621
• [Journal Article] (2008)
  • Author(s): T.Miyata, Y.Sato, J.Ishikawa, H.Okada, S.Takeshita, T.Sakata, K.Kokame, R.Kimura, S.Honda, T.Kawasaki, E.Suehisa, H.Tsuji, S.Madoiwa, Y.Sakata, T.Kojima, M.Murata, Y.Ikeda.
  • Journal Title: Thromb Res 124 Pages: 14-18
• [Presentation] インテグリン活性化におけるintegrin-linked kinaseの役割 (2010)
  • Author(s): 本田繁則、池島裕子、松田泰幸、田所誠司、冨山佳昭、宮田敏行
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20100924-20100926
• [Presentation] XXII Congress of The International Society on Thrombosis and Haemostasis (2009)
  • Author(s): 本田繁則, 池島-城谷裕子, 田所誠司, 前田祐輔, 木下タロウ, 冨山佳昭, 宮田敏行
  • Organizer: Integrin-linked kinase associated with integrin activation
  • Place of Presentation: Boston Convention & Exhibition Center (MA USA)
  • Year and Date: 2009-07-16
• [Presentation] 変異導入法を用いたインテグリン機能発現分子の同定 (2008)
  • Author(s): 本田繁則、池島-城谷裕子、田所誠司、前田祐輔、木下タロウ、冨山佳昭、宮田敏行
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 20081010-20081012
• [Remarks] ホームページ等