Activity of ternary gelatinase A-TIMP-2-matrix metallo-proteinase complexes

Abstract

The progelatinase A-TIMP-2 complex behaves like a Janus. Like TIMP (tissue inhibitor of metalloproteinases) it inhibits active matrix metalloproteinases, and activation with 4-aminophenylmercury acetate leads to a gelatinolytic activity. This activity, however, amounts only to less than 10% of that of free gelatinase A not complexed with TIMP-2. When the progelatinase A-TIMP-2 complex inhibits an active matrix metalloproteinase, a ternary complex is generated. After activation with 4-aminophenylmercury acetate this ternary complex displays a more than tenfold proteolytic activity compared to activated gelatinase A-TIMP-2 complex, thus reaching the activity of free gelatinase A. The activity of the ternary complex is nearly independent from the bound matrix metalloproteinase. When the progelatinase A-TIMP-2 complex is activated at first with 4-aminophenylmercury acetate the generation of the ternary complex is made impossible and not such a significant enhancement of activity is observed. These results suggest that gelatinase A-TIMP-2 complex may be a matrix metalloproteinase of the 'second step': It starts its proteolytic attack after it has switched off the activity of other matrix metalloproteinases.