Activation of a recombinant membrane type 1‐matrix metalloproteinase (MT1‐MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)‐2

Abstract

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.