期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 41, 页码 14911-14921出版社
ELSEVIER
DOI: 10.1074/jbc.RA119.007521
关键词
dimerization; protein phosphorylation; cell migration; laminin; epithelial cell; adhesion; Lutheran; basal cell adhesion molecule (Lu; BCAM); extracellular matrix (ECM); transmembrane protein; metastasis
资金
- Indo-French Centre for the Promotion of Advanced Research/CEFIPRA for Collaborative Grant [5302-2]
- Agence Nationale de la Recherche (SCADHESION 2007)
- Region Ile-de-France (SESAME 2007) [F-08-1104/R]
- Institut National de la Transfusion Sanguine
Tumor cell migration depends on the interactions of adhesion proteins with the extracellular matrix. Lutheran/basal cell adhesion molecule (Lu/BCAM) promotes tumor cell migration by binding to laminin ?5 chain, a subunit of laminins 511 and 521. Lu/BCAM is a type I transmembrane protein with a cytoplasmic domain of 59 (Lu) or 19 (Lu(v13)) amino acids. Here, using an array of techniques, including site-directed mutagenesis, immunoblotting, FRET, and proximity-ligation assays, we show that both Lu and Lu(v13) form homodimers at the cell surface of epithelial cancer cells. We mapped two small-XXX-small motifs in the transmembrane domain as potential sites for monomers docking and identified three cysteines in the cytoplasmic domain as being critical for covalently stabilizing dimers. We further found that Lu dimerization and phosphorylation of its cytoplasmic domain were concomitantly needed to promote cell migration. We conclude that Lu is the critical isoform supporting tumor cell migration on laminin 521 and that the Lu:Lu(v13) ratio at the cell surface may control the balance between cellular firm adhesion and migration.
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