MEMBRANE-TYPE-2 MATRIX METALLOPROTEINASE CAN INITIATE THE PROCESSING OF PROGELATINASE-A AND IS REGULATED BY THE TISSUE INHIBITORS OF METALLOPROTEINASES

Membrane-type-1 matrix metalloproteinase has been identified as an act ivator of the matrix metalloproteinase progelatinase A at cell surface s. We report here that a soluble active form of membrane-type-2 matrix metalloproteinase can also process progelatinase A in a comparable fa shion to the type-1 at rates which are dependent on the concentration of the proenzyme. Activation is inhibited by tissue inhibitors of meta lloproteinases TIMP-2 and TIMP-3, but only partially by TIMP-1. These results suggest that cellular activation of progelatinase A may be ini tiated by different members of the membrane-type matrix metalloprotein ase family depending on tissue distribution.