Open AccessActivation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases
Author(s) -
Nakamura Hiroyuki,
Fujii Yutaka,
Ohuchi Eiko,
Yamamoto Etuhide,
Okada Yasunori
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2530067.x
Subject(s) - zymogen , matrix metalloproteinase , chemistry , cleavage (geology) , extracellular matrix , stereochemistry , peptide , biochemistry , enzyme , biology , paleontology , fracture (geology)
Matrix metalloproteinases (MMP) are synthesized as inactive zymogens (proMMP) and subsequently activated by many factors to degrade the extracellular matrix (ECM). In the present study, we have examined the intermolecular activation mechanisms of proMMP by MMP‐10 (stromelysin 2). ProMMP‐10 was purified from the culture media of OSC‐20 human oral squamous carcinoma cells stimulated with 12‐ O ‐tetradecanoylphorbol 13‐acetate. The final products are partially activated (≈38 % of the full activity) during the purification steps and contain proMMP‐10 of M r 56 000 with minor protein bands of M r 47 000, 24 000 and 22 000. The zymogen is activated by 4‐aminophenylmercuric acetate and processed to the active forms of M r 47 000 and 24 000. The NH 2 ‐terminal sequence of the 47 000‐ and 24 000‐ M r species is Phe82‐Ser‐Ser‐Phe‐Pro‐Gly, which is identical to that of stromelysin 2. ProMMP‐9 (progelatinase B) is activated by MMP‐10 to its full activity and processed to the low‐ M r species of M r 81 000, 65 000, 57 000 and 55 000, the former two of which show proteolytic activity on a gelatin zymography. The NH 2 ‐terminal sequence analysis indicates that the 81 000‐, 65 000‐ and 57 000‐ M r species have the identical sequence of Phe88‐Gln‐Thr‐Phe‐Glu‐Gly, suggesting the cleavage of the Arg87−Phe88 peptide bond for activation and both NH 2 ‐terminal and COOH‐terminal truncation in the 65 000‐ and 57 000‐ M r forms. MMP‐10 also activates proMMP‐7 (promatrilysin) up to about 60 % of the full activity and generates the same active species of M r 19 000 as that obtained by activation with 4‐aminophenylmercuric acetate. Incubation of proMMP‐2 (progelatinase A) or proMMP‐3 with MMP‐10 does not result in activation of these proMMP. These results indicate that in addition to the previously reported activation of proMMP‐1 (tissue procollagenase) and proMMP‐8 (neutrophil procollagenase), MMP‐10 can also activate proMMP‐9 and proMMP‐7, and suggest the possibility that MMP‐10 may replace a role of MMP‐3 in the ECM degradation in concert with other MMP under various pathological conditions.