Article: article from journal or magazin.
Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration.
Journal of Biological Chemistry
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.
Animals, Cadherins/metabolism, Cell Adhesion Molecules/metabolism, Cell Communication, Cell Movement, Cell Transformation, Neoplastic, Cytoskeletal Proteins/metabolism, Desmoplakins, Desmosomes/metabolism, Epithelial Cells/cytology, Epithelial Cells/physiology, Humans, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis, Nerve Tissue Proteins, Phosphorylation, Protein Tyrosine Phosphatases/metabolism, Protein-Tyrosine Kinases/metabolism, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptors, Cell Surface/metabolism, Trans-Activators, Tumor Cells, Cultured, beta Catenin, gamma Catenin
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