title: A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated.
abstract: Classical cadherins associate with three cytoplasmic proteins, termed alpha, -beta- and gamma-catenin. This association mediates the attachment of cadherins to the microfilament network, which is believed to be of major importance for cadherin function. Deletion of the carboxyterminal 72-amino acid residues of E-cadherin had been previously shown to prevent catenin binding. Here we have analyzed additional mutants of E-cadherin with deletions within this region and identified a core region of 30 amino acids (E-cadherin pos. 832-862) essential for the interaction with catenins. Phosphorylation analysis of wild-type and mutant E-cadherin indicates that the catenin-binding domain is highly phosphorylated. In particular, the 30 amino acid region contains 8 serine residues which are well conserved among cadherins. To elucidate whether phosphorylation might be important for cadherin-catenin complex formation, site-directed mutagenesis experiments were performed. Partial substitutions of up to 5 of the 8 serine residues in the cluster had no influence on E-cadherin-catenin complex formation and E-cadherin mediated cell adhesion, although phosphorylation of E-cadherin was reduced. In contrast, substitution of the whole serine cluster completely abolished phosphorylation and affected complex formation with catenins. These results suggest that E-cadherin-catenin interaction may be regulated by phosphorylation of the catenin-binding domain, which might represent one molecular mechanism to regulate cadherin mediated cell adhesion.
authors: Max-Planck-Institut für Immunbiologie, Freiburg.
authors: J
authors: J
authors: Stappert
authors: R
authors: R
authors: Kemler
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051180:Desmoplakins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017384:Sequence Deletion / Q000502:physiology; D012694:Serine / Q000502:physiology; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D012694:Serine