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Analysis of the ectodomain shedding mechanism of HB-EGF

Research Project

Project/Area Number 16207014
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOsaka University

Principal Investigator

MEKADA Eisuke  Osaka University, Research Institute for Microbial Disease, Professor, 微生物病研究所, 教授 (20135742)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Ryo  Osaka University, Research Institute for Microbial Disease, Associate Professor, 微生物病研究所, 助教授 (10213323)
MIZUSHIMA Hiroto  Osaka University, Research Institute for Microbial Disease, Research Associate, 微生物病研究所, 助手 (30379094)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥51,090,000 (Direct Cost: ¥39,300,000、Indirect Cost: ¥11,790,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
KeywordsHB-EGF / ectodomain shedding / protease / ADAM / エクトドメインシェディング / シグナル伝達
Research Abstract

Ectodomain shedding is critical process for the action of heparin-binding EGF-like growth factor (HB-EGF). This process is regulated by a number of extracellular stimuli and intracellular signaling molecules. However, the molecular mechanism for ectodomain shedding has largely remained to be clarified. We found the following results :
1)Over-expression of ADAM12 mutant form with defective metalloprotease domain induced ectodomain shedding of HB-EGF in Vero cells. Over-expression of several mutant forms of ADAM12 and co-precipitation experiments with anti-ADAM12 tag antibody suggested that ADAM12 may contribute to HB-EGF shedding as an adapter protein for signaling, rather than as a protease.
2)Screening of low molecular-weight chemicals which possess the inhibitory activity for HB-EGF ectodomain shedding was performed. A few compounds showed the inhibitory activity. Further characterization is underway.
3)To understand the molecules which are involved in ectodomain shedding of HB-EGF, we constructed a screening strategy which enables to identify genes necessary for the shedding. To do this, siRNA library containing 8.4 k human genome sequence was constructed and transfected in human cells by retro virus vecter system. Cell populations which did not respond to the stimuli for shedding were isolated.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004

All Journal Article (21 results)

  • [Journal Article] Cytoplasmic Domain Phosphorylation of Heparin-Binding EGF-like Growth Factor.2006

    • Author(s)
      Wang, X.
    • Journal Title

      Cell Struct. Funct. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytoplasmic Domain Phosphorylation of Heparin-Binding EGF-like Growth Factor.2006

    • Author(s)
      Wang, X.
    • Journal Title

      Cell Struct.Funct. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytoplasmic Domain Phosphorylation of Heparin-Binding EGF-like Growth Factor.2006

    • Author(s)
      Wang, X., Mizushima, H., Adachi, S., Oishi, M., Iwamoto, R., Mekada, E.
    • Journal Title

      Cell Struct.Funct. (in press.)

    • NAID

      130004053854

    • Related Report
      2005 Annual Research Report
  • [Journal Article] HB-EGF promotes epithelial cell migration in eyelid development.2005

    • Author(s)
      Mine, N.
    • Journal Title

      Development 132

      Pages: 4317-4326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinical significance of heparin-binding epidermal growth factor-Like growth factor in peritoneal fluid of ovarian cancer.2005

    • Author(s)
      Yagi, H.
    • Journal Title

      Brit. J. Cancer 92

      Pages: 1737-1745

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.2005

    • Author(s)
      Shirakata, Y.
    • Journal Title

      J. Cell Sci. 118

      Pages: 2363-2370

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinical significance of heparin-binding EGF (epidermal growth factor)-like growth factor and ADAM (a disintegrin and metalloprotease) 17 expression in human ovarian cancer.2005

    • Author(s)
      Tanaka, T.
    • Journal Title

      Clin. Cancer Res. 11

      Pages: 4783-4792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia.2005

    • Author(s)
      Kumura, R.
    • Journal Title

      Cell Struct. Funct. 30

      Pages: 35-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinical significance of heparin-binding epidermal growth factor-Like growth factor in peritoneal fluid of ovarian cancer.2005

    • Author(s)
      Yagi, H.
    • Journal Title

      Brit.J.Cancer 92

      Pages: 1737-1745

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.2005

    • Author(s)
      Shirakata, Y.
    • Journal Title

      J.Cell Sci 118

      Pages: 2363-2370

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinical significance of heparin-binding EGF (epidermal growth factor)-like growth factor and ADAM (a disintegrin and metalloprotease) 17 expression in human ovarian cancer.2005

    • Author(s)
      Tanaka, T.
    • Journal Title

      Clin.Cancer Res 11

      Pages: 4783-4792

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia.2005

    • Author(s)
      Kimura, R.
    • Journal Title

      Cell Struct.Funct 30

      Pages: 35-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HB-EGF promotes epithelial cell migration in eyelid development.2005

    • Author(s)
      Mine, N., Iwamoto, R., Mekada, E.
    • Journal Title

      Development 132

      Pages: 4317-4326

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical significance of heparin-binding epidermal growth factor-Like growth factor in peritoneal fluid of ovarian cancer.2005

    • Author(s)
      Yagi, H., Miyamoto, S., Tanaka, Y., Sonoda, K., Kobayashi, H., Kishikawa, T., Iwamoto, R., Mekada, E., Nakano, H.
    • Journal Title

      Brit.J.Cancer 92

      Pages: 1737-1745

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.2005

    • Author(s)
      Shirakata, Y., Kimura, K., Nanba, D., Iwamoto, R., Tokumaru, S., Morimoto, C., Yokota, K., Nakamura, M., Sayama, K., Mekada, E., Higashiyama, S., Hashimoto, K.
    • Journal Title

      J.Cell Sci. 118

      Pages: 2363-2370

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical significance of heparin-binding EGF (epidermal growth factor)-like growth factor and ADAM (a disintegrin and metalloprotease) 17 expression in human ovarian cancer.2005

    • Author(s)
      Tanaka, T., Miyamoto, S., Suzuki, S.O., Oki, E., Yagi, H., Sonoda, K., Yamazaki, A., Mizushima, H., Maehara, Y., Mekada, E., Nakano, H.
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 4783-4792

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia.2005

    • Author(s)
      Kinmura, R., Iwamoto, R., Mekada, E.
    • Journal Title

      Cell Struct.Funct. 30

      Pages: 35-42

    • NAID

      130004137496

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heparin-binding EGF-like growth factor and the LPA-induced ectodomain shedding pathway is a promising target for the therapy of ovarian cancer.2004

    • Author(s)
      Miyamoto, S.他12名
    • Journal Title

      Cancer Res. 64・16

      Pages: 5720-5727

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Suppression of the biological activities of the EGF-like domain by the heparin-binding domain of heparin-binding EGF-like growth factor.2004

    • Author(s)
      Takazaki, R.他3名
    • Journal Title

      J.Biol.Chem. 279・45

      Pages: 47335-47343

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Requirement for TSP-15, a tetraspanin protein, for epidermal integrity in Caenorhabditis elegans.2004

    • Author(s)
      Moribe, H., 他4名
    • Journal Title

      J.Cell Sci. 117・22

      Pages: 5209-5220

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation.2004

    • Author(s)
      Ishibashi, T., 他6名
    • Journal Title

      J.Neurosci. 24・1

      Pages: 96-102

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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