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 activ ation of the zymogen progelatinase A/72-kDa type IV collagenase by cle avage of the Asn(66)-Leu peptide bond, We previously pointed out that MT1-MMP possesses a unique amino acid sequence Arg-Arg-Lys-Arg(111) wh ich is a potential recognition sequence for furin-like proteases (Natu re, 370 (1994) 61-65), Here, using a recombinant MT1-MMP expressed in Escherichia coli we demonstrated that furin specifically cleaves MT1-M MP between Arg(111)-Tyr in vitro, which resulted in a stimulation of p rogelatinase A-activation function, Tissue inhibitor of metalloprotein ases (TIMP)-2 inhibited activation of progelatinase A by forming a sta ble complex with activated MT1-MMP.