Abstract
Gelatinase A (MMP-2) is considered to play a critical role in cell migration and invasion. The proteinase is secreted from the cell as an inactive zymogen. In vivo it is postulated that activation of progelationase A (proMMP-2) takes place on the cell surface mediated by membrane-type matrix metalloproteinases (MT-MMPs). Recent studies have demonstrated that proMMP-2 is recruited to the cell surface by interacting with tissue in- hibitor of metalloproteinases-2 (TIMP-2) bound to MT1-MMP by forming a ternary complex. Free MT1-MMP closely located to the ternary complex then activates proMMP-2 on the cell surface. MT1-MMP is found in cultured invasive cancer cells at the invadopodia. The MT-MMP/TIMP-2/MMP-2 system thus provides localized expression of proteolysis of the extracellular matrix required for cell migration.
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This work is supported by NIH grants AR39189 and AR40994.
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Nagase, H. Cell surface activation of progelatinase A (proMMP-2) and cell migration. Cell Res 8, 179–186 (1998). https://doi.org/10.1038/cr.1998.18
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