title: Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration.
abstract: Cell migration requires precise control, which is altered or lost when tumor cells become invasive and metastatic. Although the integrity of cell-cell contacts, such as adherens junctions, is essential for the maintenance of functional epithelia, they need to be rapidly disassembled during migration. The transmembrane cell adhesion protein E-cadherin and the cytoplasmic catenins are molecular elements of these structures. Here we demonstrate that epithelial cell migration is accompanied by tyrosine phosphorylation of beta-catenin and an increase of its free cytoplasmic pool. We show further that the protein-tyrosine phosphatase LAR (leukocyte common antigen related) colocalizes with the cadherin-catenin complex in epithelial cells and associates with beta-catenin and plakoglobin. Interestingly, ectopic expression of protein-tyrosine phosphatase (PTP) LAR inhibits epithelial cell migration by preventing phosphorylation and the increase in the free pool of beta-catenin; moreover, it inhibits tumor formation in nude mice. These data support a function for PTP LAR in the regulation of epithelial cell-cell contacts at adherens junctions as well as in the control of beta-catenin signaling functions. Thus PTP-LAR appears to play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may contribute to malignant progression and metastasis.
authors: Department of Molecular Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Federal Republic of Germany. Mueller@ariad.com
authors: T
authors: T
authors: Müller
authors: A
authors: A
authors: Choidas
authors: E
authors: E
authors: Reichmann
authors: A
authors: A
authors: Ullrich
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D015815:Cell Adhesion Molecules; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D011505:Protein-Tyrosine Kinases; C516841:PTPRA protein, human; C516772:PTPRF protein, human; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; C516845:Ptpra protein, rat; C000709129:Ptprf protein, mouse; C516774:Ptprf protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4