title: Regulation of Endothelial Adherens Junctions by Tyrosine Phosphorylation.
abstract: Endothelial cells form a semipermeable, regulated barrier that limits the passage of fluid, small molecules, and leukocytes between the bloodstream and the surrounding tissues. The adherens junction, a major mechanism of intercellular adhesion, is comprised of transmembrane cadherins forming homotypic interactions between adjacent cells and associated cytoplasmic catenins linking the cadherins to the cytoskeleton. Inflammatory conditions promote the disassembly of the adherens junction and a loss of intercellular adhesion, creating openings or gaps in the endothelium through which small molecules diffuse and leukocytes transmigrate. Tyrosine kinase signaling has emerged as a central regulator of the inflammatory response, partly through direct phosphorylation and dephosphorylation of the adherens junction components. This review discusses the findings that support and those that argue against a direct effect of cadherin and catenin phosphorylation in the disassembly of the adherens junction. Recent findings indicate a complex interaction between kinases, phosphatases, and the adherens junction components that allow a fine regulation of the endothelial permeability to small molecules, leukocyte migration, and barrier resealing.
authors.affiliation: Center for Cardiovascular Sciences and Department of Ophthalmology, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Alejandro Pablo
authors.initials: AP
authors.lastname: Adam
mesh_terms: D022005:Adherens Junctions / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051177:Catenins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases