Protein Synthesis, Post-Translation Modification, and Degradation
Co-recycling of MT1-MMP and MT3-MMP through the Trans-Golgi Network: IDENTIFICATION OF DKV582 AS A RECYCLING SIGNAL*

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Members of the membrane-type matrix metalloproteinases (MT-MMPs) have been implicated in a wide range of physiological and pathological processes from normal development to tumor growth. Tethered on plasma membrane, these enzymes are potentially regulated by the trafficking machinery of the cells. Here we demonstrate that both MT1-MMP and MT3-MMP are internalized, transported to the trans-Golgi network through early endosomes, and recycled back to cell surface in 60 min in a manner distinct from the one employed by transferrin receptor. Interestingly, co-expressed MT1-MMP and MT3-MMP are localized and routed in the same vesicles throughout the trafficking process. We further demonstrated that the carboxyl-terminal sequence DKV582 of MT1-MMP is required for its recycling, thus defining a novel recycling motif. These results suggest that MT-MMPs may coordinate their proteolytic activities through the cellular trafficking machinery.

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This work was supported in part by National Institutes of Health Grant CA76308, Department of Defense Prostate Cancer Research Program Grant DAMD17-03-1-0089, American Chemical Society Grant RPG-00-056-01-CSM, and American Lung Association Grant CI-0220N. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

© 2004 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.