Matrix Metalloproteinase 7 (Matrilysin) from Human Rectal Carcinoma Cells
ACTIVATION OF THE PRECURSOR, INTERACTION WITH OTHER MATRIX METALLOPROTEINASES AND ENZYMIC PROPERTIES (*)
- Kazushi Imai(1)(3),
- Yasuo Yokohama(2),
- Isao Nakanishi(3),
- Eiko Ohuchi(4),
- Yutaka Fujii(5),
- Noboru Nakai(5) and
- Yasunori Okada(1)(§)
- From the (1)Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, Kanazawa 920, Departments of
- (2)Orthopedic Surgery and
- (3)Pathology, School of Medicine, Kanazawa University, Kanazawa 920, the
- (4)Fuji Chemical Industries, Ltd., Takaoka 933, and the
- (5)Department of Chemistry, Fukui Medical School, Fukui 910-11, Japan
- § To whom correspondence should be addressed: Dept. of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920, Japan. Tel.: 81-762-34-4507; Fax: 81-762-34-4508.
Abstract
Matrix metalloproteinase 7 (MMP-7) has been purified as an inactive zymogen of Mr 28,000 (proMMP-7) from the culture medium of CaR-1 human 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 zymogen is activated
by 4-aminophenylmercuric acetate (APMA), yielding an intermediate form of Mr 21,000 and an active species of Mr 19,000 which shows the new NH2-terminal sequence of Tyr
-Ser-Leu-Phe-Pro-Asn-Ser. Although trypsin fully activates the zymogen, the activation rate by plasmin or leukocyte elastase
is confined to 
50%. ProMMP-7 can be activated by MMP-3 (stromelysin 1) to its full activity in a single-step mechanism and generates the
same NH2 terminus obtained by APMA activation, whereas MMP-1 (tissue collagenase), MMP-2 (gelatinase A), and MMP-9 (gelatinase B)
do not have such an effect. On the 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 
6.5-fold in the presence of APMA. This enhanced activity is donated by specific cleavage at the Gln
-Phe
bond of proMMP-1. MMP-7 can also activate proMMP-9 up to 
50% of the full activity with a new NH2 terminus of Leu
-Arg-Thr-(Asn)-Leu. Incubation of proMMP-2 or proMMP-3 with MMP-7 results in no activation of these proMMPs. MMP-7 degrades
type IV collagen, laminin-1, fibronectin, proteoglycan, type I gelatin, and insoluble elastin. These results suggest that
in vivo MMP-7 may play a role in degradation of extracellular matrix macromolecules in concert with MMP-1, −3, and −9 under pathological
conditions.
Footnotes
-
↵* This work was supported by Grant-in-aid 05670167 from the ministry of Education, Science and Culture of Japan (to Y. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- MMPs
-
matrix metalloproteinases
- proMMP
-
corresponding zymogen form
- APMA
-
4-aminophenylmercuric acetate
- DIFP
-
diisopropyl fluorophosphate
- PAGE
-
polyacrylamide gel electrophoresis
- TIMP
-
tissue inhibitor of metalloproteinases
- Cm-Tf
-
carboxymethylated transferrin.
-
↵2K. Imai, A. Kimura, I. Nakanishi, and Y. Okada, unpublished data.
-
- Received October 21, 1994.
- Revision received January 18, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
