title: Beta-catenin interacts with low-molecular-weight protein tyrosine phosphatase leading to cadherin-mediated cell-cell adhesion increase.
abstract: Beta-catenin plays a dual role as a major constituent of cadherin-based adherens junctions and also as a transcriptional coactivator. In normal ephitelial cells, at adherens junction level, beta-catenin links cadherins to the actin cytoskeleton. The structure of adherens junctions is dynamically regulated by tyrosine phosphorylation. In particular, cell-cell adhesion can be negatively regulated through the tyrosine phosphorylation of beta-catenin. Furthermore, the loss of beta-catenin-cadherin association has been correlated with the transition from a benign tumor to an invasive, metastatic cancer. Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is a ubiquitous PTP implicated in the regulation of mitosis and cytoskeleton rearrangement. Here we demonstrate that the amount of free cytoplasmic beta-catenin is decreased in NIH3T3, which overexpresses active LMW-PTP, and this results in a stronger association between cadherin complexes and the actin-based cytoskeleton with respect to control cells. Confocal microscopy analysis shows that beta-catenin colocalizes with LMW-PTP at the plasma membrane. Furthermore, we provide evidence that beta-catenin is able to associate with LMW-PTP both in vitro and in vivo. Moreover, overexpression of active LMW-PTP strongly potentiates cadherin-mediated cell-cell adhesion, whereas a dominant-negative form of LMW-PTP induces the opposite phenotype, both in NIH3T3 and in MCF-7 carcinoma cells. On the basis of these results, we propose that the stability of cell-cell contacts at the adherens junction level is positively influenced by LMW-PTP expression, mainly because of the beta-catenin and LMW-PTP interaction at the plasma membrane level with consequent dephosphorylation.
authors.affiliation: Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, 50134 Florence, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Taddei
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
authors.forename: Paolo
authors.initials: P
authors.lastname: Cirri
authors.forename: Francesca
authors.initials: F
authors.lastname: Buricchi
authors.forename: Tania
authors.initials: T
authors.lastname: Fiaschi
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannoni
authors.forename: Doriana
authors.initials: D
authors.lastname: Talini
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cozzi
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raugei
authors.forename: Giampietro
authors.initials: G
authors.lastname: Ramponi
mesh_terms: D016475:3T3 Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D051176:beta Catenin; D017027:Protein Tyrosine Phosphatases