Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures.

Endothelial cell (EC) migration, cell-cell adhesion, and the formation of branching point structures are considered hallmarks of angiogenesis; however, the underlying mechanisms of these processes are not well understood. Lipid phosphate phosphatase 3 (LPP3) is a recently described p120-catenin-associated integrin ligand localized in adherens junctions (AJs) of ECs. Here, we ...
tested the hypothesis that LPP3 stimulates beta-catenin/lymphoid enhancer binding factor 1 (beta-catenin/LEF-1) to induce EC migration and formation of branching point structures. In subconfluent ECs, LPP3 induced expression of fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin homologue (PTEN)-dependent manner. In confluent ECs, depletion of p120-catenin restored LPP3-mediated beta-catenin/LEF-1 signaling. Depletion of LPP3 resulted in destabilization of beta-catenin, which in turn reduced fibronectin synthesis and deposition, which resulted in inhibition of EC migration. Accordingly, reexpression of beta-catenin but not p120-catenin in LPP3-depleted ECs restored de novo synthesis of fibronectin, which mediated EC migration and formation of branching point structures. In confluent ECs, however, a fraction of p120-catenin associated and colocalized with LPP3 at the plasma membrane, via the C-terminal cytoplasmic domain, thereby limiting the ability of LPP3 to stimulate beta-catenin/LEF-1 signaling. Thus, our study identified a key role for LPP3 in orchestrating PTEN-mediated beta-catenin/LEF-1 signaling in EC migration, cell-cell adhesion, and formation of branching point structures.
Mesh Terms:
Amino Acid Sequence, Animals, Catenins, Cell Adhesion, Cell Line, Cell Movement, Endothelial Cells, Fibronectins, Humans, Isoenzymes, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Neovascularization, Physiologic, PTEN Phosphohydrolase, Phosphatidate Phosphatase, RNA Interference, Signal Transduction, beta Catenin
Mol. Cell. Biol.
Date: Apr. 01, 2010
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