Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels

Kudo, Tomoya, Takino, Takahisa, Miyamori, Hisashi, Thompson, Erik W., & Sato, Hiroshi (2007) Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels. Cancer Science, 98(4), pp. 563-568.

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Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of matrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation.

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ID Code: 71856
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):18 Export Date: 6 May 2014 Source: Scopus PubMed ID: 17425593
Additional URLs:
DOI: 10.1111/j.1349-7006.2007.00426.x
ISSN: 1349-7006
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2007 Japanese Cancer Association
Deposited On: 20 May 2014 04:08
Last Modified: 21 May 2014 06:12

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