Format

Send to

Choose Destination
Mol Cell Biol. 2010 Apr;30(7):1593-606. doi: 10.1128/MCB.00038-09. Epub 2010 Feb 1.

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

Author information

1
Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.

Abstract

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.

PMID:
20123964
PMCID:
PMC2838065
DOI:
10.1128/MCB.00038-09
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center