Vascular endothelial cadherin phosphorylation modulates endothelial cell permeability and leukocyte transendothelial migration Public Deposited

Downloadable Content

Download PDF
Last Modified
  • March 21, 2019
  • Hart, Stephanie Hall.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Leukocyte transendothelial migration (TEM) is a key step in many functions of the immune system such as immune surveillance, inflammation and wound repair. The controlled disassembly of endothelial adherens junctions (AJs) is a major component of TEM regulation. Studies have shown the tyrosine phosphorylation of VE-cadherin, a protein important in AJs, disrupts junctions and increases vascular permeability. We found that blocking the phosphorylation of VE-cadherin on residues Y658 and Y731 using non-phosphorylatable VE-cadherin mutants lead to increased barrier function and decreased endothelial cell monolayer permeability. This demonstrates that phosphorylation of VE-cadherin residues Y658 and Y731 is necessary for the disassembly of endothelial junctions. We demonstrated that blocking phosphorylation of these residues also inhibited neutrophil transmigration across endothelial cells. Together, these data demonstrate that phosphorylation of VE-cadherin residues, Y658 and Y731, are required for the regulation of endothelial cell junction permeability and also for effective neutrophil transendothelial migration through endothelial cell monolayers.
Date of publication
Resource type
Rights statement
  • In Copyright
  • Burridge, Keith
Degree granting institution
  • University of North Carolina at Chapel Hill
  • Open access

This work has no parents.