Membrane-type-2 matrix metalloproteinase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases.

Abstract

Membrane-type-1 matrix metalloproteinase has been identified as an activator of the matrix metalloproteinase progelatinase A at cell surfaces. We report here that a soluble active form of membrane-type-2 matrix metalloproteinase can also process progelatinase A in a comparable fashion to the type-1 at rates which are dependent on the concentration of the proenzyme. Activation is inhibited by tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3, but only partially by TIMP-1. These results suggest that cellular activation of progelatinase A may be initiated by different members of the membrane-type matrix metalloproteinase family depending on tissue distribution.