Proteolytic activation of the precursor of membrane type 1 matrix metalloproteinase by human plasmin. A possible cell surface activator.
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.
Okumura
Y
Y
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Japan.
Sato
H
H
Seiki
M
M
Kido
H
H
D000595:Amino Acid Sequence; D001665:Binding Sites; D015153:Blotting, Western; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D045683:Furin; D018093:Gelatinases / Q000378:metabolism; D005982:Glutathione Transferase; D006801:Humans; D020781:Matrix Metalloproteinase 1; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism
D004792:Enzyme Precursors; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D013381:Subtilisins; D005341:Fibrinolysin; D045683:Furin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020781:Matrix Metalloproteinase 1