Abstract
The integral membrane type 1 matrix metalloprotease (MT1-MMP) is a pivotal protease in a number of physiological and pathological processes and confers both non-tumorigenic and tumorigenic cell lines with a specific growth advantage in a three-dimensional matrix. Here we show that, in a melanoma cell line, the majority (80%) of MT1-MMP is sorted to detergent-resistant membrane fractions; however, it is only the detergent-soluble fraction (20%) of MT1-MMP that undergoes intracellular processing to the mature form. Also, this processed MT1-MMP is the sole form responsible for ECM degradation in vitro. Finally, furin-dependent processing of MT1-MMP is shown to occur intracellularly after exit from the Golgi apparatus and prior to its arrival at the plasma membrane. It is thus proposed that the association of MT1-MMP with different membrane subdomains might be crucial in the control of its different activities: for instance in cell migration and invasion and other less defined ones such as MT1-MMP-dependent signaling pathways.
Original language | English |
---|---|
Pages (from-to) | 6275-87 |
Number of pages | 13 |
Journal | Journal of Cell Science |
Volume | 117 |
Issue number | Pt 26 |
DOIs | |
Publication status | Published - 15 Dec 2004 |
Keywords
- Biotinylation
- Cell Compartmentation
- Cell Line, Tumor
- Cell Movement
- Enzyme Activation
- Extracellular Matrix
- Fluorescent Antibody Technique
- Furin
- Green Fluorescent Proteins
- Humans
- Immunohistochemistry
- Matrix Metalloproteinases, Membrane-Associated
- Melanoma
- Metalloendopeptidases
- Protein Processing, Post-Translational
- Protein Structure, Tertiary
- Protein Transport