title: Regulation of VE-cadherin linkage to the cytoskeleton in endothelial cells exposed to fluid shear stress.
abstract: Endothelial cells exposed to shear stress realigned and elongated in the direction of flow through the coordinated remodeling of their adherens junctions and actin cytoskeleton. The elaborate networks of VE-cadherin complexes in static cultures became more uniform and compact in response to shear. In contrast, the cortical actin present in static cultures was reorganized into numerous stress fiber bundles distributed parallel to the direction of flow. Exposure to shear did not significantly alter the expression of the junctional proteins VE-cadherin, beta-catenin, and alpha-catenin, but the composition of the junctional complexes did change. We detected a marked decrease in the alpha-catenin associated with VE-cadherin complexes in endothelial monolayers subjected to shear. This loss of alpha-catenin, the protein that links beta-catenin-bound cadherin to the actin cytoskeleton, was not due to decreased quantities of beta-catenin associated with VE-cadherin. Instead, the loss of alpha-catenin from the junctional complexes coincided with the increased tyrosine phosphorylation of beta-catenin associated with VE-cadherin. The change in beta-catenin phosphorylation closely correlated with the shear-induced loss of the protein tyrosine phosphatase SHP-2 from VE-cadherin complexes. Thus, the functional interaction of alpha-catenin with VE-cadherin-bound beta-catenin is regulated by the extent of tyrosine phosphorylation of beta-catenin. This, concomitantly, is regulated by SHP-2 associated with VE-cadherin complexes.
authors.affiliation: Department of Physiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Ukropec
authors.forename: M Katherine
authors.initials: MK
authors.lastname: Hollinger
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Woolkalis
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013314:Stress, Mechanical; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D015534:Trans-Activators; D014443:Tyrosine; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human