Matrix Metalloproteinase-2 Is an Interstitial Collagenase
INHIBITOR-FREE ENZYME CATALYZES THE CLEAVAGE OF COLLAGEN FIBRILS AND SOLUBLE NATIVE TYPE I COLLAGEN GENERATING THE SPECIFIC ¾- AND ¼-LENGTH FRAGMENTS (*)
- From the (1)Department of Biochemistry and Cell Biology and
- (2)Department of Pathology, State University of New York, Stony Brook, New York 11794
- ¶ To whom correspondence should be addressed. Tel.: 516-444-3014; Fax: 516-444-3424.
Abstract
The 72-kDa gelatinase/type IV collagenase (MMP-2) is a member of the matrix metalloproteinase (MMP) family of enzymes. This
enzyme is known to cleave type IV collagen as well as degrade denatured collagens. However, native interstitial collagens
are reportedly resistant to MMP-2 and are thought to be susceptible only to the interstitial collagenases MMP-1 and MMP-8.
In this study we report that both human and chicken MMP-2, free of tissue inhibitors of metalloproteinases (TIMPs) are capable
of cleaving soluble, triple helical type I collagen generating the ¾- and ¼-length collagen fragments characteristic of vertebrate
interstitial collagenases. MMP-2 cleaves at the same Gly-Ile/Leu bond in the collagen α chains as interstitial collagenases
with k
and K
values similar to that of MMP-1. MMP-2 also is capable of degrading reconstituted type I collagen fibrils. The closely related
92-kDa gelatinase/type IV collagenase (MMP-9) is unable to cleave soluble or fibrillar collagen under identical conditions
indicating that the specific collagenolytic activity of MMP-2 is not a general property of gelatinases. That MMP-2, a potent
gelatinase, also can cleave fibrillar collagen provides an alternative to the proposal that two enzymes, an interstitial collagenase
and a gelatinase, are required for the complete dissolution of stromal collagen during cellular invasion.
Footnotes
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↵§ Institute for Cell and Developmental Biology predoctoral scholar supported by a fellowship from Merck and Company.
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↵* This work was supported in part by United States Public Health Service Grant CA 55852 (to J. P. Q.). 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.
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↵1 The abbreviations used are:
- ECM
-
extracellular matrix
- MMP
-
matrix metalloproteinase
- TIMP
-
tissue inhibitor of metalloproteinases
- APMA
-
p-aminophenylmercuric acetate
- PAGE
-
polyacrylamide gel electrophoresis
- TC
-
tropocollagen
- TPCK
-
L-1-tosylamido-2-phenylethyl chloromethyl ketone.
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- Received November 18, 1994.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
