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Updated: Jul 5, 2026

Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
Published on: December 20, 2017
Nuclear targeting of beta-catenin and p120ctn during thrombin-induced endothelial barrier dysfunction
Cora M L Beckers1, Juan J García-Vallejo, Victor W M van Hinsbergh
1Department for Physiology, VU University Medical Center, Institute for Cardiovascular Research, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Aims:
Cytosolic and nuclear localization of beta-catenin was observed in leaky vessels and in tumours. Several lines of evidence indicate that nuclear beta-catenin facilitates angiogenesis. We hypothesized that nuclear beta-catenin liberated from endothelial junctional complexes marks the transition from hyperpermeability to angiogenesis. The aim of this study was, therefore, to investigate the fate of beta-catenin and the related catenin p120catenin (p120ctn), during disruption of the endothelial barrier function in human umbilical vein endothelial cells (ECs).
Methods And Results:
The hyperpermeability-inducer thrombin caused a Rho kinase-dependent redistribution of beta-catenin from the membrane to the cytosol as evidenced by the western blot analysis of membrane and cytosol fractions and by immunohistochemistry. Glycogen synthase kinase 3beta, which phosphorylates cytosolic beta-catenin and thereby facilitates its proteasomal degradation, was inhibited by thrombin. The analysis of nuclear extracts demonstrated a thrombin-induced nuclear accumulation of beta-catenin as well as p120ctn. Thrombin stimulation activated beta-catenin-mediated transcriptional activity as evidenced by reporter assays. Finally, real-time-PCR revealed increased mRNA levels of several beta-catenin target genes.
Conclusion:
Thrombin induced a cytosolic stabilization of membrane-liberated beta-catenin, which, together with p120ctn, subsequently translocated to the nucleus where it induces several beta-catenin target genes. This supports the suggestion that membrane-liberated beta-catenin and p120ctn contribute to angiogenic responses of ECs following episodes of vascular leakage.
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