Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Among the five membrane-type matrix metalloproteinases (MT-MMPs), MT1-, MT2-, MT3-, and MT5-MMPs have about a 20-amino acid cytoplasmic tail following the transmembrane domain. In contrast, a putative transmembrane domain of MT4-MMP locates at the very C-terminal end, and the expected cytoplasmic tail is very short or nonexistent. Such sequences often act as a glycosylphosphatidylinositol (GPI) anchoring signal rather than as a transmembrane domain. We thus examined the possibility that MT4-MMP is a GPI-anchored proteinase. Our results showed that [(3)H]ethanolamine, which 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 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.

Original publication




Journal article


The Journal of biological chemistry

Publication Date





34260 - 34266


Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.


COS Cells, CHO Cells, Animals, Humans, Mice, Tritium, Ethanolamine, Thiophenes, Phosphatidylinositol Diacylglycerol-Lyase, Endopeptidases, Metalloendopeptidases, Matrix Metalloproteinases, Glycosylphosphatidylinositols, Phenylalanine, Recombinant Fusion Proteins, Protease Inhibitors, Microscopy, Confocal, Fluorescent Antibody Technique, Indirect, Sequence Alignment, Binding Sites, Amino Acid Sequence, Molecular Sequence Data, Cricetinae, Matrix Metalloproteinases, Membrane-Associated, Type C Phospholipases, Phosphoinositide Phospholipase C