Abstract
In several pathological conditions, epithelial cells demonstrate a breakdown of barrier function and acquire an invasive phenotype. Endothelial cells in particular are maintained in a mesenchymal state during the cell invasion phase of angiogenesis. We show here that tyrosine phosphorylation of the adherens junction protein VE-cadherin at two critical tyrosines, Tyr-658 and Tyr-731, via tyrosine kinase activation or phosphatase inactivation was sufficient to prevent the binding of p120- and beta-catenin, respectively, to the cytoplasmic tail of VE-cadherin. In fact, phosphorylation at either site led to the inhibition of cell barrier function. Cells expressing wild-type VE-cadherin showed decreased cell migration compared with cells lacking VE-cadherin, whereas expression of VE-cadherin with a simple phosphomimetic tyrosine-to-glutamic acid mutation of Y658E or Y731E was sufficient to restore the migratory response. These findings demonstrate that a single phosphorylation event within the VE-cadherin cytoplasmic tail is sufficient to maintain cells in a mesenchymal state.
Highlights
Cadherins are important regulators of a number of epithelial cell barriers [1]
To determine whether phosphorylation of one or more of these sites might play a role in cadherin function, wild-type VE-cadherin and VE-cadherin containing phosphomimetic tyrosine-to-glutamic acid mutations were stably expressed in CHO cells lacking endogenous cadherins
These findings reveal that both Tyr-658 and Tyr-731 can regulate VE-cadherin-mediated cell barrier function
Summary
Cadherins are important regulators of a number of epithelial cell barriers [1]. While allowing cells to maintain impermeable cell monolayers, cadherins act to prevent epithelial cell motility. Tyrosine phosphorylation of the cadherin cytoplasmic tail or its catenin binding partners is thought to regulate cadherin adhesion and cell surface expression (16 – 21).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have