Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase

J Biol Chem. 1999 Nov 26;274(48):34260-6. doi: 10.1074/jbc.274.48.34260.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Endopeptidases / drug effects
  • Endopeptidases / metabolism
  • Ethanolamine / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Matrix Metalloproteinases / chemistry
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases*
  • Mice
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphoinositide Phospholipase C
  • Protease Inhibitors / pharmacology
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / genetics
  • Sequence Alignment
  • Thiophenes / pharmacology
  • Tritium
  • Type C Phospholipases / pharmacology

Substances

  • Glycosylphosphatidylinositols
  • Protease Inhibitors
  • Recombinant Fusion Proteins
  • Thiophenes
  • Tritium
  • Phenylalanine
  • Ethanolamine
  • batimastat
  • Type C Phospholipases
  • Phosphoinositide Phospholipase C
  • Endopeptidases
  • MMP17 protein, human
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Mmp17 protein, mouse
  • Phosphatidylinositol Diacylglycerol-Lyase