• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Characterization of the structure and function of new membrane-type matrix metalloproteinase

Research Project

Project/Area Number 10680596
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo Institute of Medical Science

Principal Investigator

ITOH Yoshifumi  Institute of Medical sciences, University of Tokyo, Dept. of Cancer cell Research, Assistant Professor, 医科学研究所, 助手 (70292852)

Project Period (FY) 1998 – 1999
KeywordsMMP / MT-MMP / GPI
Research Abstract

One of the 5 MT-MMP members, MT4-MMP, was originally identified by cDNA cloning from breast carcinoma cell line by Puente at al. (Cancer Res. 56, 944-949, 1996). However, the coding region for a signal peptide, which exists in all MMP family members, is substituted with an unknown sequence in the cDNA, and it could not direct expression of the gene product in the transfected cells. In contrast, we isolated a mouse and human mt4-mmp (mt4-mmp(m)) gene that can direct expression of the gene product by having a coding region for a signal peptide. The Puente's sequence was minor transcript representing only 1/10 of the total mt4-mmp mRNA and found to be derived from an aberrant splicing product for the first intron. Thus, we have isolated a major functional transcripts of MT4-MMP.
A putative transmembrane domain of MT4-MMP locates at the very C-terminal end while others have an about 20 aminoacids cytoplasmic domain following the transmembrane domain. Such sequences often act as a glycosyl-phosphatidyl inositol (GPI) anchoring signal rather than as a transmembrane domain, suggesting the possibility that MT4-MMP is a GPI-anchored proteinase. Our result showed that [3H] ethanolamine, that can be incorporated into the GPI unit, specifically labeled the MT4-MMP C-terminal end in a sequence dependent manner. In addition, phosphatidylinositol-specific phospholipase C (PI-PLC) treatment released the MT4-MMP from the surface of transfected cells. These results indicate that MT4-MMP is the first GPI-anchored proteinase in the MMP family. During cultivation of the transfected cells, MT4-MMP appeared to be shed from the cell surface by the action of an endogenous metalloproteinase. GPI-anchoring of MT4-MMP on the cell surface indicates a unique biological function and character for this proteinase.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Itoh, Y., et al.: "Membrane-type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosyl-phosphatidyl 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
  • [Publications] Kajita, M., et al.: "Human Membrane Type-4 Matrix Metalloproteinase (MT4-MMP) is encoded by a novel major transcript: Isolation of complementary DNA clones for human and mouse nt4-mmp transcripts"FEBS Letter. 457. 353-356 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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."Cytogenet Cell Genet.. 87. 97-98 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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-->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
  • [Publications] Kajita M. et al.: "Human Membrane Type-4 Matrix Metalloproteinase (MT4-MMP) is encoded by a novel major transcript : Isolation of complementary DNA clones for human and mouse mt4-mmp transcripts."FEBS Letter. 457. 353-356 (1999)

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

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

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi