Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration

J Biol Chem. 1999 Apr 9;274(15):10173-83. doi: 10.1074/jbc.274.15.10173.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cell Adhesion Molecules
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Desmoplakins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Trans-Activators
  • beta Catenin
  • gamma Catenin
  • Protein-Tyrosine Kinases
  • PTPRA protein, human
  • PTPRF protein, human
  • Protein Tyrosine Phosphatases
  • Ptpra protein, mouse
  • Ptpra protein, rat
  • Ptprf protein, mouse
  • Ptprf protein, rat
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4