title: Tyrosine phosphorylation translocates beta-catenin from cell-->cell interface to the cytoplasm, but does not significantly enhance the LEF-1-dependent transactivating function.
abstract: beta-catenin plays an essential role in cells, not only as a cadherin-associated complex, but also as a signaling molecule in the nucleus. Tyrosine phosphorylation of beta-catenin has been shown to correlate with tumorigenesis, cell migration, and developmental processes. However, its exact effects on downstream targets in the nucleus are not yet clear. In this study, we used HCT-15 colon carcinoma and NIH 3T3 fibroblasts as models to investigate the effects of a phosphotyrosine phosphatase (PTPase) inhibitor on the localization of beta-catenin, the binding affinity to LEF-1 (Lymphoid Enhancer Factor), and on LEF-1-dependent transactivation function. Treatment with a PTPase inhibitor, pervanadate, increased the tyrosine phosphorylation of beta-catenin in a time-dependent manner and led to its relocation from cell-cell interfaces to the cytoplasm. This phosphorylation/dephosphorylation of beta-catenin does not require its presence at cell-cell interfaces. However, tyrosine phosphorylation of beta-catenin does not change its binding affinity to LEF-1 nor enhance cyclin D1 transactivation, a nuclear target of beta-catenin/LEF-1. This result suggests that tyrosine phosphorylation of beta-catenin has effects on the binding to cadherins in the cytoplasm but not on its LEF-1-dependent transactivating function in the nucleus.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston MA 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: K Y
authors.initials: KY
authors.lastname: Lee
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D003110:Colonic Neoplasms; D019938:Cyclin D1 / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C076715:pervanadate; D019938:Cyclin D1; D014638:Vanadates; D014443:Tyrosine; D008156:Luciferases; D017027:Protein Tyrosine Phosphatases