MATRIX METALLOPROTEINASE-7 (MATRILYSIN) FROM HUMAN RECTAL-CARCINOMA CELLS - ACTIVATION OF THE PRECURSOR, INTERACTION WITH OTHER MATRIX METALLOPROTEINASES AND ENZYMATIC-PROPERTIES

Matrix metalloproteinase 7 (MMP-7) has been purified as an inactive zy mogen of M(r), 28,000 (proMMP-7) from the culture medium of CaR-1 huma n rectal carcinoma cells. The NH2-terminal sequence of proMMP-7 is Lys -Pro-Lys-Pro-Gln-Glu, which is identical to that of matrilysin. The zy mogen is activated by 4-aminophenylmercuric acetate (APMA), yielding a n intermediate form of M(r) 21,000 and an active species of M(r) 19,00 0 which shows the new NH2-terminal sequence of Tyr(78)-Ser-Leu-Phe-Pro -Asn-Ser. Although trypsin fully activates the zymogen, the activation rate by plasmin or leukocyte elastase is confined to similar to 50%. ProMMP-7 can be activated by MMP-3 (stromelysin 1) to its full activit y in a single-step mechanism and generates the same NH2 terminus obtai ned by APMA activation, whereas MMP-1 (tissue collagenase), MMP-2 (gel atinase A), and MMP-9 (gelatinase B) do not have such an effect, On th e other hand, proMMP-1 is activated by MMP-7 to an activity similar to that obtained by APMA and the activation by MMP-7 is enhanced up to s imilar to 6.5 fold in the presence of APMA, This enhanced activity is donated by specific cleavage at the Gln(80)-Phe(81) bond of proMMP-1. MMP-7 can also activate proMMP-9 up to similar to 50% of the full acti vity with a new NH2 terminus of Leu(16)-Arg-Thr-(Asn)-Leu. Incubation of proMMP-2 or proMMP-3 with MMP-7 results in no activation of these p roMMPs. MMP-7 degrades type IV collagen, laminin-1, fibronectin, prote oglycan, type I gelatin, and insoluble elastin, These results suggest that in vivo MMP-7 may play a role in degradation of extracellular mat rix macromolecules in concert with MMP-1, -3, and -9 under pathologica l conditions.