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Dimerization and phosphorylation of Lutheran/basal cell adhesion molecule are critical for its function in cell migration on laminin.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2019 Oct 11; Vol. 294 (41), pp. 14911-14921. Date of Electronic Publication: 2019 Aug 14. - Publication Year :
- 2019
-
Abstract
- 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 α5 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.<br /> (© 2019 Guadall et al.)
- Subjects :
- Amino Acid Sequence
Animals
Caco-2 Cells
Dogs
Humans
Madin Darby Canine Kidney Cells
Models, Molecular
Phosphorylation drug effects
Protein Domains
Protein Structure, Quaternary
Cell Adhesion Molecules chemistry
Cell Adhesion Molecules metabolism
Cell Movement drug effects
Laminin pharmacology
Lutheran Blood-Group System chemistry
Lutheran Blood-Group System metabolism
Protein Multimerization drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 294
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31413112
- Full Text :
- https://doi.org/10.1074/jbc.RA119.007521