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| INTERACTION OF 92-KDA TYPE-IV COLLAGENASE WITH THE TISSUE INHIBITOR OF METALLOPROTEINASES PREVENTS DIMERIZATION, COMPLEX-FORMATION WITH INTERSTITIAL COLLAGENASE, AND ACTIVATION OF THE PROENZYME WITH STROMELYSIN |
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| Author(s): GOLDBERG GI, STRONGIN A, COLLIER IE, GENRICH LT, MARMER BL |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 267 Issue: 7 Pages: 4583-4591 Published: MAR 5 1992 |
| Times Cited: 397 References: 48 |
| Abstract: Secreted metalloproteases initiating proteolytic degradation of collagens and proteoglycans play a critical role in remodeling of the connective tissue. Activation of the secreted proenzymes and interaction with their specific inhibitors TIMP and TIMP-2 are responsible for regulation of enzyme activity in extracellular space. We have previously demonstrated that 92- and 72-kDa Type IV procollagenases, in contrast to interstitial collagenase (ClI), form specific complexes with TIMP and the related inhibitor TIMP-2, respectively. The physiologic significance of the proenzyme-inhibitor complex and the mechanism of activation of Type IV collagenases remained unclear. Here, we demonstrate that in the absence of TIMP, 92-kDa Type IV procollagenase (92T4Cl) can form a covalent homodimer and a novel complex with ClI. In the presence of TIMP, the formation of a 92T4Cl proenzyme complex with TIMP prevents dimerization, formation of the complex with ClI, and activation of the 92T4Cl proenzyme by stromelysin, a related metalloprotease. The proenzyme homodimer is unable to form a complex with TIMP. All TIMP-free forms of the proenzyme can be activated by stromelysin. The 92T4Cl-ClI complex can be activated to yield a complex active against both gelatin and fibrillar Type I collagen, suggesting a mechanism for cooperative action of two enzymes in reducing collagen fibrils to small peptides under physiologic conditions.
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| Document Type: Article |
| Language: English |
| Reprint Address: GOLDBERG, GI (reprint author), WASHINGTON UNIV, SCH MED, DIV DERMATOL, ST LOUIS, MO 63110 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: HF642 |
| ISSN: 0021-9258 |
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