ACTIVITY OF TERNARY GELATINASE A-TIMP-2-MATRIX METALLOPROTEINASE COMPLEXES

The progelatinase A-TIMP-2 complex behaves like a Janus. Like TIMP (ti ssue inhibitor of metalloproteinases) it inhibits active matrix metall oproteinases, and activation with 4-aminophenylmercury acetate leads t o a gelatinolytic activity. This activity, however, amounts only to le ss than 10% of that of free gelatinase A not complexed with TIMP-2. Wh en the progelatinase A-TIMP-2 complex inhibits an active matrix metall oproteinase, a ternary complex is generated, After activation with 4-a minophenylmercury acetate this ternary complex displays a more than te nfold proteolytic activity compared to activated gelatinase A-TIMP-2 c omplex, thus reaching the activity of free gelatinase A. The activity of the ternary complex is nearly independent from the bound matrix met alloproteinase. When the progelatinase A-TIMP-2 complex is activated a t first with 4-aminophenylmercury acetate the generation of the ternar y 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 sta rts its proteolytic attack after it has switched off the activity of o ther matrix metalloproteinases.