| First Author | Wang P | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 19 | Pages | 20461-70 |
| PubMed ID | 14990567 | Mgi Jnum | J:212810 |
| Mgi Id | MGI:5582176 | Doi | 10.1074/jbc.M400264200 |
| Citation | Wang P, et al. (2004) Mint-3 regulates the retrieval of the internalized membrane-type matrix metalloproteinase, MT5-MMP, to the plasma membrane by binding to its carboxyl end motif EWV. J Biol Chem 279(19):20461-70 |
| abstractText | Membrane type matrix metalloproteinases (MT-MMPs) play a critical role in promoting cell growth and migration within the extracellular matrix by trafficking to specialized areas. Here we show that the carboxyl EWV motif of MT5-MMP serves as a retrieval signal for internalized MT5-MMP by interacting with Mint-3, a protein with two type III PDZ domains. Deletion of the EWV signal impairs the recycling of MT5-MMP without affecting its internalization, leading to decreased activity on the cell surface. A yeast two-hybrid screening identified Mint-3 as the EWV-binding protein. Mint-3 stimulates MT5-MMP activity when expressed at low levels in an EWV-dependent fashion, but inhibits its activity at higher levels independent of the EWV motif. siRNA-mediated knockdown of endogenous Mint-3 decreased MT5-MMP activity. Furthermore, Mint-3 significantly increased the level of MT5-MMP on the cell surface without affecting its synthesis and internalization. Therefore, Mints may be the adaptor proteins that regulate the trafficking of MT-MMPs. |
