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Isolation and analysis of new memnrane-type matrix metalloproteinases

Research Project

Project/Area Number 10470028
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

SEIKI Motoharu  Univ. Tokyo, Inst. Med. Sci., Prof., 医科学研究所, 教授 (10154634)

Co-Investigator(Kenkyū-buntansha) ITOH Yoshifumi  Univ. Tokyo, Inst. Med. Sci., Assis. Prof., 医科学研究所, 助手 (70292852)
OKADA Akiko  Univ. Tokyo, Inst. Med. Sci., Assis. Prof., 医科学研究所, 助手 (00233320)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥10,000,000 (Direct Cost: ¥10,000,000)
KeywordsMMP / MT-MMP / GPI / マトリックスメタロプロテアーゼ / 膜型酵素 / がんの浸潤・転移 / MT4-MMP / 細胞外基質分解酵素
Research Abstract

1. At the beginning of this study, four distinct membrane-type matrix metalloproteinases (MT-MMPs) has been identified. Since the fourth member, MT4-MMP, lacks signal peptide sequence in the reported DNA, we re-analyzed transcripts for MT4-MMP in human and mouse cells. In human, two types of the transcripts were identified and one corresponded to the previously reported one. The other transcript was found to encode signal peptide a part of propeptide sequence that was missing in the previously reported one. Thus, functional gene was firstly identfied. Similarly, mouse cDNA was also identified.
2. The carboxy terminal region of MT4-MMP is distantly related to other MT-MMP membaers that have a hydrophobic amino acid streatch acting transmembrane domain. Although the C-terminal amino acids of MT4-MMP is also hydrophobic, it was demonstarted that the sequence was a signal for processing and for glycosyal phosphatidial inositol anchoring.
3. Fifth member of MT-MMP group was identified by cDNA cloning. It was found to be expressed selectively in cereberum and thoght to be important for the development and maintenance of central nervous system.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Itoh, Y. et al.: "Membrane-type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidyl inositol (GPI)-anchored proteinase"J. Biol. Chem.. 274. 34260-34266 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kajita, M. et al.: "Human Membrane Type-4 Matrix Metalloproteinase (MT4-MMP) is encoded by a novel major transcript"FEBS Letter. 457. 353-356 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kinoh, H. et al.: "Assignment(1) of the genes for membrane-type-4 matrix metalloproteinase (Mmp17, MMP17) to mouse chromosome 5, human chromosome band 12q24.3 and membrane-type-5 matrix metalloproteinase (Mmp24, MMP24) to mouse chromosome 2 and human chromosome band 20q11.2"Cytogenet Cell Genet. 87. 97-98 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Afzal, S. et al.: "MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts"Hum Pathol. 29. 155-165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cha, H.J. et al.: "Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells"Oncogene. 16. 771-778 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, Y., M. Kajita, H. Kinoh, H. Mori, A. Okada, and M. Seiki: "Membrane Type 4 Matrix Metalloproteinase (MT4-MMP, MMP-l7) Is a Glycosylphosphatidylinositol-anchored Proteinase"J Biol Chem. 274. 34260-34266 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kajita, M., H. Kinoh. N. Ito, A. Takamura, A. Okada, H. Sato, and M. Seiki: "Human membrane type-4 matrix metalloproteinase (MT4-MMP) is en-coded by a novel major transcript isolation of complementary DNA clones for human and mouse mt4-mmp transcripts"FEBS Lett. 457. 353-356 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kinoh, H., H. Hayashita, M. Kajita, A. Okada and M. Seiki: "Assignment (1) of the genes for nembmne-type4 matrix metalloproteinase (Mmp 17, MMP17) to mouse chromosome 5, human chromosome band 12q24.3 and membrane-type-5 matrix metalloproteinase (Mmp24. MMP24) to mouse chromosome 2 and human Chromosome band 20ql1.2->ql2, respectively, by radiation hybrid and in situ hybridization"Cytogenet Cell Genet. 87. 97-98 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Afzal, S., E. N. Lalani, R. Poulsom, A. Stubbs. G. Rowlinson, H. Sato, M. Seiki, and G. W. Stamp: "MT1-MMP and MMP-2 mRNA expression in human ovarian tumors : possible implications for the role of desmoplastic fibroblasts"Hum Pathol. 29. 155-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cha, H. J., M. T. Park, H. Y. Chung, N. D. Kim, H. Sato, M. Seki, and K. W. Kim: "Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT 1080 human fibrosarcoma cells"Oncogene. 16. 771-778 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh,Y et al.: "Membrance-type 4 matrix metalloproteinase(MT4-MMP,MMP-17) is a gycosylphosphatidyl inositol (GPI)-anchored proteinase"J.Biol.Chem.. 274. 34260-34266 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kajita,M.et al.: "Human Membrance Type-4 Matrix Metalloproteinase (MT4-MMP) is encoded by a novel major transcript"FEBS Letter. 457. 353-356 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 清木 元治: "Membrane Type 1-Matrix Metalloproteinase is involved in the formation of hepatocyte growth factor/scatter factor-induced branching tubules in madin-darby canine kidney epithelial calls." Biochem.Biophys.Res.Commun.251. 681-687 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清木 元治: "Expression of the membrane-type 3 matrix metalloproteinase(MT3-MMP)in human brain tissues." Acta neuropathol.96. 347-350 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清木 元治: "New Collagenolytic Enzymes/Cascade identified at the pannus-hard tissue junction in rheumatoid arthritis." Matrix Biology. 17. 585-601 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清木 元治: "Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis." Oncol.Rep.5. 1485-1488 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清木 元治: "Overexpression of tissue inhibitor of matrix metalloproteinase-1(TIMP-1)in metastatic MDCK cells transformed by v-src." Clin.Exp.Metastasis. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清木 元治: "MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts." Human Pathology. 29. 155-165 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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