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Am J Physiol Cell Physiol 283: C811-C821, 2002; doi:10.1152/ajpcell.00417.2001
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Vol. 283, Issue 3, C811-C821, September 2002

Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and beta -catenin

Kala Venkiteswaran1,*, Kanyan Xiao1,*, Susan Summers1, Cathárine C. Calkins1, Peter A. Vincent2, Kevin Pumiglia3, and Andrew P. Kowalczyk1

1 Departments of Dermatology, Cell Biology, and Emory Skin Diseases Research Center, Emory University School of Medicine, Atlanta, Georgia 30322; and 2 Center for Cardiovascular Sciences and 3 Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York 12208

VE-cadherin is an endothelial-specific cadherin that plays a central role in vascular barrier function and angiogenesis. The cytoplasmic domain of VE-cadherin is linked to the cytoskeleton through interactions with the armadillo family proteins beta -catenin and plakoglobin. Growing evidence indicates that beta -catenin and plakoglobin play important roles in epithelial growth and morphogenesis. To test the role of these proteins in vascular cells, a replication-deficient retroviral system was used to express intercellular junction proteins and mutants in the human dermal microvascular endothelial cell line (HMEC-1). A mutant VE-cadherin lacking an adhesive extracellular domain disrupted endothelial barrier function and inhibited endothelial growth. In contrast, expression of exogenous plakoglobin or metabolically stable mutants of beta -catenin stimulated HMEC-1 cell growth, which suggests that the beta -catenin signaling pathway was active in HMEC-1 cells. This possibility was supported by the finding that a dominant-negative mutant of the transcription factor TCF-4, designed to inhibit beta -catenin signaling, also inhibited HMEC-1 cell growth. These observations suggest that intercellular junction proteins function as components of an adhesion and signaling system that regulates vascular barrier function and growth.

adherens junction; angiogenesis; Wnt signaling

* K. Venkiteswaran and K. Xiao contributed equally to this work.




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