title: E-cadherin is a ligand for integrin alpha2beta1.
abstract: E-cadherin is a 120-kDa transmembrane glycoprotein expressed mainly on the surface of epithelial cells. The best characterised function of E-cadherin is homotypic, calcium-dependent cell-cell adhesion; however, the observation that E-cadherin is also capable of interacting with the alphaEbeta7 integrin to mediate leukocyte cell-cell adhesion [Nature 372 (1994) 190] suggests that it also participates in heterotypic interactions. To investigate the possibility that E-cadherin may interact with integrins expressed on non-leukocytic cells, cell adhesion and solid-phase receptor-ligand binding experiments were performed using a pentameric E-cadherin construct designed to detect low affinity, high avidity interactions. HT1080 human fibrosarcoma cells specifically adhered to pentameric E-cadherin, and this adhesion was inhibited by anti-functional monoclonal antibodies directed against the integrin alpha2 and beta1 subunits, but not by a series of antibodies recognising other subunits. This suggested that the E-cadherin receptor was alpha2beta1, a previously characterised collagen/laminin receptor. Pentameric E-cadherin, but not monomeric E-cadherin, specifically bound, in a divalent cation-dependent manner, to both purified alpha2beta1 and to a recombinant form of the A-domain of the alpha2 subunit, which has been shown to be a major ligand-binding site within this and other integrins. These findings demonstrate that E-cadherin can interact with alpha2beta1 and suggest that heterotypic interactions between E-cadherin and integrins may be more common than originally thought.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Whittard
authors.forename: Susan E
authors.initials: SE
authors.lastname: Craig
authors.forename: A Paul
authors.initials: AP
authors.lastname: Mould
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Olivier
authors.initials: O
authors.lastname: Pertz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Engel
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D015820:Cadherins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008024:Ligands; D017434:Protein Structure, Tertiary / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D038982:Integrin alpha2beta1; D008024:Ligands; D011994:Recombinant Proteins