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

TY - JOUR

T1 - Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration.

AU - Anilkumar, Narayanapanicker

AU - Uekita, Takamasa

AU - Couchman, John R

AU - Nagase, Hideaki

AU - Seiki, Motoharu

AU - Itoh, Yoshifumi

N1 - 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

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1096/fj.04-3651fje

DO - 10.1096/fj.04-3651fje

M3 - Journal article

C2 - 15946988

SN - 0892-6638

VL - 19

SP - 1326

EP - 1328

JO - The FASEB Journal

JF - The FASEB Journal

IS - 10

ER -