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| MATRIX METALLOPROTEINASE-9 (92-KDA GELATINASE TYPE-IV COLLAGENASE) FROM HT-1080 HUMAN FIBROSARCOMA CELLS - PURIFICATION AND ACTIVATION OF THE PRECURSOR AND ENZYMATIC-PROPERTIES |
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| Author(s): OKADA Y, GONOJI Y, NAKA K, TOMITA K, NAKANISHI I, IWATA K, YAMASHITA K, HAYAKAWA T |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 267 Issue: 30 Pages: 21712-21719 Published: OCT 25 1992 |
| Times Cited: 400 References: 54 |
| Abstract: Matrix metalloproteinase 9 (MMP-9) has been purified as an inactive zymogen of M(r) 92,000 (proMMP-9) from the culture medium of HT 1080 human fibrosarcoma cells. The NH2-terminal sequence of proMMP-9 is Ala-Pro-Arg-Gln-Arg-Gln-Ser-Thr-Leu-Val-Leu-Phe-Pro, which is identical to that of the 92-kDa type IV collagenase/gelatinase. The zymogen can be activated by 4-aminophenylmercuric acetate, yielding an intermediate form of M(r) 83,000 and an active species of M(r) 67,000, the second of which has a new NH2 terminus of Met-Arg-Thr-Pro-Arg-(Cys)-Gly-Val-Pro-Asp-Leu-Gly-Arg-Phe-Gln-Thr-Phe-Glu. Immunoblot analyses demonstrate that this activation process is achieved by sequential processing of both NH2- and COOH-terminal peptides. TIMP-1 complexed with proMMP-9 inhibits the conversion of the intermediate form to the active species of M(r) 67,000. The proenzyme is fully activated by cathepsin G, trypsin, alpha-chymotrypsin, and MMP-3 (stromelysin 1) but not by plasmin, leukocyte elastase, plasma kallikrein, thrombin, or MMP-1 (tissue collagenase). During the activation by MMP-3, proMMP-9 is converted to an active species of M(r) 64,000 that lacks both NH2- and COOH-terminal peptides. In addition, HOCl partially activates the zymogen by reacting with an intermediate species of M(r) 83,000. The enzyme degrades type I gelatin rapidly and also cleaves native collagens including alpha2 chain of type I collagen, collagen types III, IV, and V at undenaturing temperatures. These results indicate that MMP-9 has different activation mechanisms and substrate specificity from those of MMP-2 (72-kDa gelatinase/type IV collagenase). |
| Document Type: Article |
| Language: English |
| Reprint Address: OKADA, Y (reprint author), KANAZAWA UNIV, SCH MED, DEPT PATHOL, 13-1 TAKARA MACHI, KANAZAWA, ISHIKAWA 920 JAPAN |
Addresses:
1. KANAZAWA UNIV, SCH MED, DEPT ORTHOPED SURG, KANAZAWA, ISHIKAWA 920 JAPAN
2. FUJI CHEM IND CO LTD, TAKAOKA 933, JAPAN
3. AICHI GAKUIN UNIV, SCH DENT, DEPT BIOCHEM, NAGOYA 464, JAPAN |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: JV011 |
| ISSN: 0021-9258 |
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