Protein-tyrosine phosphatase PCP-2 inhibits beta-catenin signaling and increases E-cadherin-dependent cell adhesion.
beta-Catenin is a key molecule involved in both cell adhesion and Wnt signaling pathway. However, the exact relationship between these two roles has not been clearly elucidated. Tyrosine phosphorylation of beta-catenin was shown to decrease its binding to E-cadherin, leading to decreased cell adhesion and increased beta-catenin signaling. We have ... previously shown that receptor-like protein-tyrosine phosphatase PCP-2 localizes to the adherens junctions and directly binds and dephosphorylates beta-catenin, suggesting that PCP-2 might regulate the balance between signaling and adhesive beta-catenin. Here we demonstrate that PCP-2 can inhibit both the wild-type and constitutively active forms of beta-catenin in activating target genes such as c-myc. The phosphatase activity of PCP-2 is required for this effect since loss of catalytic activity attenuates its inhibitory effect on beta-catenin activation. Expression of PCP-2 in SW480 colon cancer cells can lead to stabilization of cytosolic pools of beta-catenin perhaps, by virtue of their physical interaction. PCP-2 expression also leads to increased membrane-bound E-cadherin and greater stabilization of adherens junctions by dephosphorylation of beta-catenin, which could further sequester cytosolic beta-catenin and thus inhibit beta-catenin mediated nuclear signaling. Furthermore, SW480 cells stably expressing PCP-2 have a reduced ability to proliferate and migrate. Thus, PCP-2 may play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may be an alternative mechanism for activating beta-catenin signaling.
Mesh Terms:
Base Sequence, Cadherins, Cell Adhesion, Cell Line, Cell Proliferation, Cytoplasm, Genes, myc, Humans, Membranes, Mutagenesis, Site-Directed, Phosphorylation, Protein Tyrosine Phosphatases, RNA, Small Interfering, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Recombinant Proteins, Signal Transduction, Transcriptional Activation, Transfection, beta Catenin
Base Sequence, Cadherins, Cell Adhesion, Cell Line, Cell Proliferation, Cytoplasm, Genes, myc, Humans, Membranes, Mutagenesis, Site-Directed, Phosphorylation, Protein Tyrosine Phosphatases, RNA, Small Interfering, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Recombinant Proteins, Signal Transduction, Transcriptional Activation, Transfection, beta Catenin
J. Biol. Chem.
Date: Jun. 02, 2006
PubMed ID: 16574648
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