title: An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation.
abstract: The cadherins are a family of adhesive proteins involved in cell-cell homophilic interactions. VE-cadherin, expressed in endothelial cells, is involved in morphogenesis, regulation of permeability, and cellular proliferation. The cytoplasmic tails of cadherins contain two major domains, the juxtamembrane domain that plays a role in the intercellular localization of the protein and also serves for binding of p120ctn, and a C-terminal domain that associates with beta- or gamma-catenin. A highly conserved region present in the juxtamembrane domain of the cadherins has been shown to be necessary for p120ctn binding in E-cadherin. Using a mutant VE-cadherin lacking a highly conserved octapeptide, we demonstrated that it is required for p120ctn binding to VE-cadherin as determined by immunoprecipitation and colocalization studies. By immunofluorescence, this mutant protein has a topographical distribution similar to that of the wild-type VE-cadherin and, therefore, we conclude that the topographical distribution of VE-cadherin is independent of this motif. In addition, although cell-cell association is present in cells expressing this mutant form of VE-cadherin, we found that the strength of adhesion is decreased. Finally, our results for the first time demonstrate that the interaction of VE-cadherin with p120 catenin plays an important role in cellular growth, suggesting that the binding of p120 catenin to cadherins may regulate cell proliferation.
authors.affiliation: Cardeza Foundation for Hematological Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5099, USA. andres.ferber@mail.tju.edu
authors.forename: Andres
authors.initials: A
authors.lastname: Ferber
authors.forename: Christopher
authors.initials: C
authors.lastname: Yaen
authors.forename: Edna
authors.initials: E
authors.lastname: Sarmiento
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D016466:CHO Cells; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division; D017124:Conserved Sequence; D006224:Cricetinae; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014162:Transfection; D000095002:Delta Catenin; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010446:Peptide Fragments; D010750:Phosphoproteins; D000095002:Delta Catenin; D000099152:Cadherin 5