E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.
beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin and also with the tumor suppressor gene product APC, and the Drosophila homologue of beta-catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E-cadherin and APC directly compete for binding to the internal, armadillo-like repeats of beta-catenin; the NH2-terminal domain of beta-catenin mediates the interaction of the alternative E-cadherin and APC complexes to the cytoskeleton by binding to alpha-catenin. Plakoglobin (gamma-catenin), which is structurally related to beta-catenin, mediates identical interactions. We thus show that the APC tumor suppressor gene product forms strikingly similar associations as found in cell junctions and suggest that beta-catenin and plakoglobin are central regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.
Hülsken
J
J
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Birchmeier
W
W
Behrens
J
J
D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D051180:Desmoplakins; D005455:Fluorescent Antibody Technique; D007365:Intercellular Junctions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D011994:Recombinant Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin