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2001 Fiscal Year Final Research Report Summary

Regulatory mechanism of β3 integrin function via signaling molecules

Research Project

Project/Area Number 12470201
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

TOMIYAMA Yoshiaki  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80252667)

Co-Investigator(Kenkyū-buntansha) KASHIWAGI Hirokazu  Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
ORITANI Kenji  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70324762)
HONDA Shigenori  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00303959)
Project Period (FY) 2000 – 2001
Keywordsβ_3 integrin / Megakaryocyte / Inside-out signaling / NCX
Research Abstract

β_3 integrins, which contain α_<IIb>β_3 and α_vβ_3, play critical roles in atherosclerosis as well as thrombosis. Therefore, the elucidation of the regulatory mechanisms for integrin function is a critical issue to control these vascular events. In this research project, we have tried to establish a new experimental model other than platelets to examine the regulation of β_3 integrin function.
Firstly, we have analyzed structural and functional analyses of αvβ_3 integrin. Based on the β-propeller model we have examined ligand-binding sites in the αv subunit employing alanine-scanning mutagenesis. We demonstrated that 178Tyr in the W3 2-3 loop is one of the critical residues for ligand-binding. Secondly, we have examined early megakaryocytes derived from umbilical cord blood mononuclear cells and certain megakaryocytic cell lines and demonstrated that CD42b(GPIb)-positive cells could activate α_<IIb>β_3 within several minutes after TRAP and/or PMA stimulation. We have been searching molecules responsible for integrin activation employing differential display method between CD42b-positive and CD42b-negative cells in a certain megakaryocytic cell line. Thirdly, we have examined Na^+/Ca^<2+> exchanger in platelets which we have firstly demonstrated as an important signaling molecule for integrin activation. We demonstrated a new 70 kD isoform in platelets instead of 110-kD form. The functional significance of the 70 kD NCX is under investigation.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tomiyama Y: "Glanzmann thrombasthenia : integrin aIIbb3 deficiency. (A review)"Int J Hematol. 72. 448-454 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida H, Tomiyama Y, et al.: "Integrin-associated protein/CD47 regulates motile activity in human B cell lines through CDC42"Blood. 96. 234-241 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kosugi S, Tomiyama Y, et al.: "Anti-αvβ3 antibodies in chronic immune thrombocytopenia"Thromb Haemost. 85. 36-41 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kashiwagi H, Tomiyama Y, et al.: "Analyses of genetic abnormalities in type i CD36 deficiency in Japan : identification and cell biological characterization of two novel mutations that cause CD36 deticiency in man"Human Genetics. 108. 459-466 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kosugi S, Tomiyama Y, et al.: "Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of glycoprotein(GP)IIb"Blood. 98. 1819-1827 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tadokoro S, Tomiyama Y, et al.: "Missense mutations in the β3 subunit have a different impact on the expressin and function between αIIbβ3 and αvβ3"Blood. 99. 931-938 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomiyama Y: "Glanzmann thrombasthenia : integrin αIIbβ3 deficiency. (A review)"Int J Hematol. 72 (4). 448-454 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida H, Tomiyama Y, et al: "Integrin-associated protein/CD47 regulates motile activity in human B cell lines through CDC42"Blood. 96(1). 234-241 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kosugi S, Tomiyama Y, et al: "Anti-αvβ3 antibodies in chronic immune thrombocytopenia"Thromb Haemost. 85 (1). 36-41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi H, Tomiyama Y, et al.: "Analyses of genetic abnormalities in type I CD36 deficiency in Japan : identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man"Human Genetics. 108 (6). 459-466 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kosugi S, Tomiyama Y, et al: "Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of glycoprotein(GP) IIb"Blood. 98 (6). 1819-1827 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tadokoro S, Tomiyama Y, et al: "Missense mutations in the β3 subunit have a different impact on the expression and function between αIIbβ3 and avb3"Blood. 99 (3). 931-938 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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