Proteolytic activation of the precursor of membrane type 1 matrix metalloproteinase by human plasmin. A possible cell surface activator

FEBS Lett. 1997 Feb 3;402(2-3):181-4. doi: 10.1016/s0014-5793(96)01523-2.


Membrane type 1 matrix metalloproteinase (MT1-MMP) was suggested to play a critical role in the regulation of tissue invasion by normal and neoplastic cells by directly mediating the activation of pro-gelatinase A. Recently, the proteolytic activation of a pro-MT1-MMP by an intracellular proprotein convertase, furin, was reported. In this study, we found that plasmin efficiently activates the pro-MT1-MMP by cleaving immediately downstream of Arg108 and Arg111 in the multi-basic motif between its pro- and catalytic domains that participates in the activation of pro-gelatinase A. Our present data suggest that pro-MT1-MMP transported to the plasma membrane is activated by plasmin extracellularly and thus it may play an important role in the matrix degradation process.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Blotting, Western
  • Collagenases / chemistry
  • Collagenases / metabolism*
  • Enzyme Activation
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / metabolism*
  • Fibrinolysin / metabolism*
  • Furin
  • Gelatinases / metabolism
  • Glutathione Transferase
  • Humans
  • Matrix Metalloproteinase 1
  • Metalloendopeptidases / metabolism
  • Molecular Sequence Data
  • Protease Inhibitors / pharmacology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Subtilisins / metabolism


  • Enzyme Precursors
  • Protease Inhibitors
  • Recombinant Fusion Proteins
  • Glutathione Transferase
  • Subtilisins
  • Fibrinolysin
  • Furin
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • progelatinase
  • Matrix Metalloproteinase 1