Protein kinase C modifications of VE-cadherin, p120, and beta-catenin contribute to endothelial barrier dysregulation induced by thrombin
Φόρτωση...
Ημερομηνία
Συγγραφείς
Konstantoulaki, M.
Kouklis, P.
Malik, A. B.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Am J Physiol Lung Cell Mol Physiol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The adherens junction is a multiprotein complex consisting of the transmembrane vascular endothelial cadherin (VEC) and cytoplasmic catenins (p120, beta-catenin, plakoglobin, alpha-catenin) responsible for the maintenance of endothelial barrier function. Junctional disassembly and modifications in cadherin/catenin complex lead to increased paracellular permeability of the endothelial barrier. However, the mechanisms of junctional disassembly remain unclear. In this study, we used the proinflammatory mediator thrombin to compromise the barrier function and test the hypothesis that phosphorylation-induced alterations of VEC, beta-catenin, and p120 regulate junction disassembly and mediate the increased endothelial permeability response. The study showed that thrombin induced dephosphorylation of VEC, which is coupled to disassembly of cell-cell contacts, but VEC remained in aggregates at the plasma membrane. The cytoplasmic catenins dissociated from the VEC cytoplasmic domain in thin membrane projections formed in interendothelial gaps. We also showed that thrombin induced dephosphorylation of beta-catenin and phosphorylation of p120. Thrombin-induced interendothelial gap formation and increased endothelial permeability were blocked by protein kinase C inhibition using chelerythrine and Go-6976 but not by LY-379196. Chelerythrine also prevented thrombin-induced phosphorylation changes of the cadherin/catenin complex. Thus the present study links posttranslational modifications of VEC, beta-catenin, and p120 to the mechanism of thrombin-induced increase in endothelial permeability.
Περιγραφή
Λέξεις-κλειδιά
Alkaloids, Antigens, CD, Benzophenanthridines, Cadherins/*metabolism, Carbazoles/pharmacology, Catenins, Cell Adhesion/drug effects/physiology, Cell Adhesion Molecules/*metabolism, Cell Membrane/drug effects/physiology, Cells, Cultured, Cytoskeletal Proteins/*metabolism, Endothelium, Vascular/cytology/drug effects/*physiology, Enzyme Inhibitors/pharmacology, Humans, Indoles/pharmacology, Kinetics, Mesylates/pharmacology, Phenanthridines/pharmacology, Phosphoproteins/*metabolism, Protein Kinase C/*metabolism, Protein Processing, Post-Translational, Pulmonary Artery/*physiology, Pyrroles/pharmacology, Thrombin/*pharmacology, Trans-Activators/*metabolism, beta Catenin
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/12740216
http://ajplung.physiology.org/content/285/2/L434.full.pdf
http://ajplung.physiology.org/content/285/2/L434.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής