Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels
Data(s) |
2007
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Resumo |
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. |
Formato |
application/pdf |
Identificador | |
Publicador |
Wiley Open Access |
Relação |
http://eprints.qut.edu.au/71856/1/71856%28pub%29.pdf DOI:10.1111/j.1349-7006.2007.00426.x 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. |
Direitos |
Copyright 2007 Japanese Cancer Association |
Fonte |
Faculty of Health |
Tipo |
Journal Article |