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

Kala Venkiteswaran, Kanyan Xiao, Susan Summers, Cathárine C. Calkins, Peter A. Vincent, Kevin Pumiglia, Andrew P. Kowalczyk

Research output: Contribution to journalArticle

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Abstract

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 β-catenin and plakoglobin. Growing evidence indicates that β-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 β-catenin stimulated HMEC-1 cell growth, which suggests that the β-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 β-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number3 52-3
StatePublished - Sep 2002

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gamma Catenin
Catenins
Blood Vessels
Growth
Intercellular Junctions
Armadillo Domain Proteins
TCF Transcription Factors
Mutant Proteins
Cadherins
Cytoskeleton
Morphogenesis
Adhesives
Proteins
Endothelial Cells
cadherin 5
Cell Line
Skin

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Venkiteswaran, K., Xiao, K., Summers, S., Calkins, C. C., Vincent, P. A., Pumiglia, K., & Kowalczyk, A. P. (2002). Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin. American Journal of Physiology - Cell Physiology, 283(3 52-3).
Venkiteswaran, Kala ; Xiao, Kanyan ; Summers, Susan ; Calkins, Cathárine C. ; Vincent, Peter A. ; Pumiglia, Kevin ; Kowalczyk, Andrew P. / Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin. In: American Journal of Physiology - Cell Physiology. 2002 ; Vol. 283, No. 3 52-3.
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Venkiteswaran, K, Xiao, K, Summers, S, Calkins, CC, Vincent, PA, Pumiglia, K & Kowalczyk, AP 2002, 'Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin', American Journal of Physiology - Cell Physiology, vol. 283, no. 3 52-3.

Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin. / Venkiteswaran, Kala; Xiao, Kanyan; Summers, Susan; Calkins, Cathárine C.; Vincent, Peter A.; Pumiglia, Kevin; Kowalczyk, Andrew P.

In: American Journal of Physiology - Cell Physiology, Vol. 283, No. 3 52-3, 09.2002.

Research output: Contribution to journalArticle

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AU - Venkiteswaran, Kala

AU - Xiao, Kanyan

AU - Summers, Susan

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AU - Vincent, Peter A.

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AU - Kowalczyk, Andrew P.

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