Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2.
Membrane type 1-matrix metalloproteinase (MT1-MMP) initiates the activation of the zymogen progelatinase A/ 72-kDa type IV collagenase by cleavage of the Asn66-Leu peptide bond. We previously pointed out that MT1-MMP possesses a unique amino acid sequence Arg-Arg-Lys-Arg111 which is a potential recognition sequence for furin-like proteases (Nature, 370 (1994) 61-65). Here, using a recombinant MT1-MMP expressed in Escherichia coli we demonstrated that furin specifically cleaves MT1-MMP between Arg111-Tyr in vitro, which resulted in a stimulation of progelatinase A-activation function. Tissue inhibitor of metalloproteinases (TIMP)-2 inhibited activation of progelatinase A by forming a stable complex with activated MT1-MMP.
Sato
H
H
Department of Molecular Virology and Oncology, Kanazawa University, Japan. vhsato@kenroku.ipc.kanazawa-u.ac.jp
Kinoshita
T
T
Takino
T
T
Nakayama
K
K
Seiki
M
M
D001120:Arginine; D001665:Binding Sites; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors; D045683:Furin; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000494:pharmacology; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013381:Subtilisins / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D014443:Tyrosine
D004792:Enzyme Precursors; D006023:Glycoproteins; D011480:Protease Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D013876:Thiophenes; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D014443:Tyrosine; D010649:Phenylalanine; D001120:Arginine; C080985:batimastat; D013381:Subtilisins; D045683:Furin; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase