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The role of membrane-anchored HB-EGF on cell growth

Research Project

Project/Area Number 09044348
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Cell biology
Research InstitutionKurume University

Principal Investigator

MEKADA Eisuke  Kurume University, PROFESSOR, 分子生命科学研究所, 教授 (20135742)

Co-Investigator(Kenkyū-buntansha) KLAGSBRUN Michael  Kurume University, PROFESSOR, チルドレンズホスピタル, 教授
SEKIGUCHI Kiyotoshi  Kurume University, PROFESSOR, 所長 (50187845)
UMATA Toshiyuki  Kurume University, ASSISTANT PROFESSOR, 分子生命科学研究所, 助手 (30213482)
IWAMOTO Ryo  Kurume University, ASSISTANT PROFESSOR, 分子生命科学研究所, 助手 (10213323)
TSUNEOKA Makoto  Kurume University, ASSISTANT PROFESSOR, 分子生命科学研究所, 講師 (50197745)
中村 邦明  久留米大学, 分子生命科学研究所, 日本学術振興会特別研
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsHB-EGF / CD9 / Integrin / Cell adhesion / Growth Factors / アポトーシス / ジャクスタクライン
Research Abstract

HB-EGF is a member of EGF family growth factors. The membrane-anchored form of HB- EGF (proHB-EGF) is also known to be a diphtheria toxin receptor. Therefore this protein is a kind of membrane-anchored growth factors in one hand, the specific receptor of the bacteria toxin in the other hand. Dr. Klagsbrun identified HIB-EGF in the cell culture medium and studied biological activities of the soluble form of HB-EGF, while Mekada have studied proHB-EGF as the diphtheria toxin receptor. The aim of this joint meeting is to examine the physiological roles of proHB-EGF in cell growth and developmental processes.
ProHB-EGP forms a complex with other membrane proteins. CD9 and heparan-sulfate proteoglycan(s) associate with proHB-EGF and modulate its biological activities. ProHB-EGF also forms a complex with integrincalpha3beta1. Studies by immunofluorescence staining showed that the complex cornprised of proHB-EGF, CD9 and integrina#3beta1 co-localizes at cell-cell contact sites, suggesting that … More the proHB-EGF complex plays a role in intercellular communication in a juxtacrine manner. In order to know the physiological role of the proHB-EGF complex in a intercellular communication, we have done the following studies and got the results as follows :
1)Upregulation of proHB-EGF activity by CD9 : CD9 upregulates the biological activities of proHB-EGF.Regions in both CD9 and proHB-EGF necessary for the upregulation were determined.
2)Growth inhibitory activity of proHB-EGF : We have observed that proHB-EGF shows growth inhibitory activity by juxtacrine mechanism under the culture conditions which soluble forms of HB-EGF and EGF stimulate cell growth. Thus, it is suggested that the soluble form and the membrane-anchored form have different biological activities for cell growth control.
3)Analysis of CD9 null mice : CD9 would have a key role to connect proHB-EGF with integrinalpha3beta1 . To analyze the physiological role of proHB-EGF complex CD9 null mice were generated. CD9 null mice were born and seem healthy, but showed severe defect in reproductive system. Further studies are now in progress. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Izumi, Y: "A metalloprotease-disintegrin, MDC9/Meltring-g/ADM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-Like growth factor." EMBO J.17. 7260-7272 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuneoka, M.: "N-myc transactivates RCCI gene expression in rat fibroblast cells transformed by N-myc and v-ras." J. Biochem.124. 1013-1019 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Umata,T.: "Diphtheria toxin translocation across endosome membrane. A novel cell permeabilization assay reveals new diphtheria toxin fragments in endocytic vesicles." J. Biol. Chem.273. 8351-8359 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mitamura, T.: "Structure-function analysis of the diphtheria toxin receptor toxin binding site by site-directed mutagenesis." J. Biol. Chem.272. 27084-27090 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuneoka, M.: "c-myc activates RCCI gene expression through E-box elements." Oncogene. 14. 2301-2311 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kagawa, T: "Immune system-related CD9 is expressed in mouse central nervous system myelin at a very late stage of myelination." J. Neurosci. Res.50. 312-320 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 岩本 亮: "医学&サイエンスシリーズ 細胞接着のしくみと疾患" 羊土社, 7 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumi, Y.: "A metalloprotease-disintegrin, MDC9/Meltrin-g/ADM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor" EMBO J.17. 7260-7272 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuneoka, M.: "N-mycc transactivates RCC1 geneexpression in rat fibroblast cells transformed by N-myc and v-ras" J.Biochem.124. 1013-1019 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Umata, T.: "Diphtheria toxin translocation across endosome membrane.A novel cell permeabilization assay reveals new diphtheria toxin fragments in endocytic vesicles" J.Biol.Chem.273. 8351-8359 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mitamura, T.: "Structure-function analysis of the diphtheria toxin receptor toxin binding site by site-directed mutagenesis." J.Biol.Chem.272. 27084-27090 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuneoka, M: "c-myc activates RCC1 geneexpression through E-box elements" Oncogene. 14. 2301-2311 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kagawa, T.: "Immune system-related CD9 is expressed in mouse central nervous system myelin at a very late stage of myelination." J.Neurosci.Res.50. 312-320 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumi, Y.: "A metalloprotease-disintegrin, MDC9/Meltrin-g/ADM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor." EMBO J.17. 7260-7272 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuneoka, M.: "N-myc transactivates RCC1 gene expression in rat fibroblast cells transformed by N-myc and v-ras." J.Biochem.124. 1013-1019 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Umata, T.: "Diphtheria toxin translocation across endosome membrane. A novel cell permeabilization assay reveals new diphtheria toxin fragments in endocytic vesicles." J.Biol.Chem.273. 8351-8359 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 岩本 亮: "医学&サイエンスシリーズ 細胞接着のしくみと疾患" 羊土社, 7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Umata, T.: "Diphtheria toxin translocation across endosome membranes:A novel cell permeabilization assay reveals new DT fragments in endocytic vesicles." J.Biol.Chem.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Mitamura, T.: "Structure-Function Analysis of the Diphtheria Toxin Receptor Toxin Binding Site by Site-directed Mutagenesis." J.Biol.Chem.272. 27084-27090 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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