title: Allosteric Regulation of E-Cadherin Adhesion.
abstract: Cadherins are transmembrane adhesion proteins that maintain intercellular cohesion in all tissues, and their rapid regulation is essential for organized tissue remodeling. Despite some evidence that cadherin adhesion might be allosterically regulated, testing of this has been hindered by the difficulty of quantifying altered E-cadherin binding affinity caused by perturbations outside the ectodomain binding site. Here, measured kinetics of cadherin-mediated intercellular adhesion demonstrated quantitatively that treatment with activating, anti-E-cadherin antibodies or the dephosphorylation of a cytoplasmic binding partner, p120(ctn), increased the homophilic binding affinity of E-cadherin. Results obtained with Colo 205 cells, which express inactive E-cadherin and do not aggregate, demonstrated that four treatments, which induced Colo 205 aggregation and p120(ctn) dephosphorylation, triggered quantitatively similar increases in E-cadherin affinity. Several processes can alter cell aggregation, but these results directly demonstrated the allosteric regulation of cell surface E-cadherin by p120(ctn) dephosphorylation.
authors.affiliation: From the Departments of Biochemistry.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Shashikanth
authors.affiliation: the Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, and.
authors.forename: Yuliya I
authors.initials: YI
authors.lastname: Petrova
authors.affiliation: Physics, and.
authors.forename: Seongjin
authors.initials: S
authors.lastname: Park
authors.affiliation: Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Illinois 61801.
authors.forename: Jillian
authors.initials: J
authors.lastname: Chekan
authors.affiliation: the Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Maiden
authors.affiliation: the Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, and.
authors.forename: Martha
authors.initials: M
authors.lastname: Spano
authors.affiliation: From the Departments of Biochemistry, Physics, and the Howard Hughes Medical Institute, Urbana, Illinois 61801.
authors.forename: Taekjip
authors.initials: T
authors.lastname: Ha
authors.affiliation: the Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, and.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Gumbiner
authors.affiliation: From the Departments of Biochemistry, Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Illinois 61801, leckband@illinois.edu.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Leckband
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D004285:Dogs; D006801:Humans; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology; D061986:MCF-7 Cells; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D000095002:Delta Catenin
chemical_list: D057134:Antibodies, Neutralizing; D015820:Cadherins; D051177:Catenins; D050505:Mutant Proteins; D018021:Lithium Chloride; D019311:Staurosporine; D000095002:Delta Catenin
keywords: allosteric regulation; cadherin-1 (CDH1) (epithelial cadherin) (E-cadherin); catenin; cell adhesion; kinetics