Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase.
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.
Itoh
Y
Y
Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Kajita
M
M
Kinoh
H
H
Mori
H
H
Okada
A
A
Seiki
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism; D019856:Ethanolamine / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011480:Protease Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D013876:Thiophenes / Q000494:pharmacology; D014316:Tritium; D010738:Type C Phospholipases / Q000494:pharmacology
D017261:Glycosylphosphatidylinositols; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D013876:Thiophenes; D014316:Tritium; D010649:Phenylalanine; D019856:Ethanolamine; C080985:batimastat; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D010450:Endopeptidases; C402225:MMP17 protein, human; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C498537:Mmp17 protein, mouse; D043265:Phosphatidylinositol Diacylglycerol-Lyase