Identification of signaling molecules associated with β3 integrins using random mutagenesis

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591095
• 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, National Cardiovascular Center Research Institute, Senior Staff (00303959)
• Co-Investigator(Kenkyū-buntansha): MIYATA Toshiyuki National Cardiovascular Center Research Institute, 病因部, Director (90183970) ; TOMIYAMA Yoshiaki Osaka University Hospital, 医学部附属病院・輸血部, Assistant Professor (80252667)
• Project Period (FY): 2006 – 2007
• Keywords: integrin / signaling molecule / platelet

Research Abstract

We established cell line expressing chimeric integrin αIIbα6Bβ3 energy-dependently activated. To obtain signaling defective mutant cells that express inactivated αIIbα6Bβ3, the cell line was treated with a chemical mutagen, EMS. Next, we performed expression cloning in which the mutant clone was transfected with cDNA library, and integrin-linked kinase(ILK) was isolated as a molecule induced activation of inactivated αIIbα6Bβ3 in the mutant. Imunoblot analysis showed that the mutant lacked ILK protein. ILK gene in the mutant contained two different nonsense mutations at a compound heterozygous state. ILK knockdown in a parental cell not treated with EMS significantly suppressed integrin activation.

Research Products

• [Journal Article] Genotypes of vitamin K epoxide reductase,γ-glutamyl carboxylase,andcytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. (2007)
  • Author(s): Kimura R, , Miyashita K, Kokubo Y, Akaiwa Y, Ryoichi O, Nagatsuka K, Otsuki T, Okayama A, Minematsu K, Naritomi H, Honda S, Tomoike H, Miyata T
  • Journal Title: Thromb Res 120 Pages: 181-186
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. (2007)
  • Author(s): Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T
  • Journal Title: Thromb Haemost 98 Pages: 783-789
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. (2007)
  • Author(s): Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T
  • Journal Title: Thromb Haemost 98-4 Pages: 783-789
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. (2006)
  • Author(s): F Banno, K Kokame, T Okuda, S Honda, S Miyata, H Kato,Y Tomiyama, T Miyata
  • Journal Title: Blood 107-8 Pages: 3161-3166
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adiponectin acts as an endogenous antithrombotic factor. (2006)
  • Author(s): Kato H, Kashiwagi H, Shiraga M, Tadokoro S, Kamae T, Ujiie H, Honda S, Miyata S, Ijiri Y, Yamamoto J, Maeda N, Funahashi T,Kurata Y, Shimomura I, Tomiyama Y, Kanakura Y
  • Journal Title: Anterioscler Thromb Vasc Biol 26-1 Pages: 224-230
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. (2007)
  • Author(s): Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T
  • Organizer: Congress of the Japanese Society on Thrombosis Hemostasis
  • Place of Presentation: Mie
  • Year and Date: 20071115-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Effects of complete deficiency and C-terminal deletion of ADAMTS13 on hemostatic function in mice (2007)
  • Author(s): Fumiaki Banno, Koichi Kokame, Tomohiko Okuda, Shigenori Honda, Shigeki Miyata, Hisashi Kato, Yoshiaki Tomiyama, Toshiyuki Miyata
  • Organizer: International Mammalian Genome Conference
  • Place of Presentation: Kyoto
  • Year and Date: 20071028-1101
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. (2007)
  • Author(s): Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T
  • Organizer: 第30回日本血栓止血学会学術集会
  • Place of Presentation: 賢島宝生苑・志摩観光ホテル
  • Year and Date: 2007-11-16
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ADAMTS13 and its related issues, invited lecture (2006)
  • Author(s): Toshiyuki Miyata
  • Organizer: Gordon Research Conference
  • Place of Presentation: Waterville, ME, USA.
  • Year and Date: 2006-07-11
  • Description: 「研究成果報告書概要(欧文)」より