Processing of a precursor of 72-kilodalton type IV collagenase/gelatinase A by a recombinant membrane-type 1 matrix metalloproteinase.
Membrane-type 1 matrix metalloproteinase that is associated with the proteolytic activation of progelatinase A was expressed as a recombinant fusion protein in Escherichia coli. The recombinant enzyme cleaved the propeptide sequence of gelatinase A in a sequence-specific manner. A mutant progelatinase A that has a substitution of Asn(66)-Leu to Ile-Val was not processed at all. The processing was blocked by tissue inhibitor of metalloproteinases-2 or BB-94 but not by tissue inhibitor of metalloproteinases-1. Thus, membrane-type 1 matrix metalloproteinase is a direct activator of progelatinase A without requiring additional proteases.
Kinoshita
T
T
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Japan.
Sato
H
H
Takino
T
T
Itoh
M
M
Akizawa
T
T
Seiki
M
M
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D018093:Gelatinases / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000494:pharmacology; D011993:Recombinant Fusion Proteins; D013876:Thiophenes / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011498:Protein Precursors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D013876:Thiophenes; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D010649:Phenylalanine; C080985:batimastat; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1