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.
Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan.
T
T
Ohkubo
M
M
Ozawa
D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000502:physiology*; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D017384:Sequence Deletion; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse