Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration.

Journal article

MT1-MMP is a type I transmembrane proteinase that promotes cell migration and invasion. Here, we report that MT1-MMP is palmitoylated at Cys574 in the cytoplasmic domain, and this lipid modification is critical for its promotion of cell migration and clathrin-mediated internalization. The palmitoylation-defective mutant (C574A) failed to promote cell migration and was not internalized through clathrin pathway like wild-type, but it was internalized through the caveolae pathway. Reintroducing a cysteine at different positions in the cytoplasmic tail of the C574A mutant revealed that the position of the palmitoylated cysteine relative to LLY573, a motif that interacts with mu2 subunit of adaptor protein 2, is critical for the cell motility-promoting activity of MT1-MMP and its clathrin-mediated internalization. Taken together, palmitoylation of MT1-MMP is one of the key posttranslational modifications that determines MT1-MMP-dependent cell migration.

Authors: Anilkumar, N; Uekita, T; Couchman, JR; Nagase, H; Seiki, M

• Publication status: Published
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• Volume: 19
• Issue: 10
• Pages: 1326-1328
• Publication date: 2005-08-01
• DOI: 10.1096/fj.04-3651fje
• EISSN: 1530-6860
• ISSN: 0892-6638
• Language: English
• Keywords: Cricetinae; Cell Movement; Cysteine; Mice; Palmitic Acid; COS Cells; CHO Cells; Amino Acid Motifs; Matrix Metalloproteinase 14; Protein Processing, Post-Translational; Animals; Clathrin; Caveolae; Matrix Metalloproteinases, Membrane-Associated; Matrix Metalloproteinases; Cercopithecus aethiops