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

Research output: Contribution to journalJournal articleResearchpeer-review

Narayanapanicker Anilkumar, Takamasa Uekita, John R Couchman, Hideaki Nagase, Motoharu Seiki, Yoshifumi Itoh

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.
Original languageEnglish
JournalThe FASEB Journal
Volume19
Issue number10
Pages (from-to)1326-8
Number of pages2
ISSN0892-6638
DOIs
Publication statusPublished - 2005

Bibliographical note

Keywords: Amino Acid Motifs; Animals; CHO Cells; COS Cells; Caveolae; Cell Movement; Cercopithecus aethiops; Clathrin; Cricetinae; Cysteine; Matrix Metalloproteinase 14; Matrix Metalloproteinases; Matrix Metalloproteinases, Membrane-Associated; Mice; Palmitic Acid; Protein Processing, Post-Translational

ID: 5160926