p120(ctn) binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity.
Cadherins are transmembrane glycoproteins involved in Ca(2+)-dependent cell-cell adhesion. Previously, we showed that the conserved membrane-proximal region of the E-cadherin cytoplasmic domain negatively regulates adhesion activity. In this report, we provide several lines of evidence that p120(ctn) is involved in this negative regulation. p120(ctn) binds to the membrane-proximal region of ... the nonfunctional carboxyl-terminally deleted E-cadherin protein. An additional internal deletion in this region prevented the association with p120(ctn) and activated the protein, as seen in an aggregation assay. Furthermore, the nonfunctional E-cadherin can be activated through coexpression of p120(ctn) proteins with amino-terminal deletions, which eliminate several potential serine/threonine phosphorylation sites but do not affect the ability to bind to cadherins. Finally, we show that staurosporine, a kinase inhibitor, induces an increased electrophoretic mobility of p120(ctn) bound to E-cadherin polypeptides, activates the nonfunctional E-cadherin protein, and converts the wild-type E-cadherin and an E-cadherin-alpha-catenin chimeric protein from a cytochalasin D-sensitive to a cytochalasin D-insensitive state. Together, these results indicate that p120(ctn) is a modulator of E-cadherin-mediated cell adhesion.
Mesh Terms:
Animals, Base Sequence, Cadherins, Cell Adhesion, Cell Adhesion Molecules, Cell Membrane, Fibroblasts, Mice, Molecular Sequence Data, Phosphoproteins, Sequence Deletion
Animals, Base Sequence, Cadherins, Cell Adhesion, Cell Adhesion Molecules, Cell Membrane, Fibroblasts, Mice, Molecular Sequence Data, Phosphoproteins, Sequence Deletion
J. Biol. Chem.
Date: Jul. 23, 1999
PubMed ID: 10409703
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