VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells.
Blood-flow interactions with the vascular endothelium represents a specialized example of mechanical regulation of cell function that has important physiological and pathophysiological cardiovascular consequences. Yet, the mechanisms of mechanostransduction are not understood fully. This study shows that shear stress induces a rapid induction as well as nuclear translocation of the vascular endothelial growth factor (VEGF) receptor 2 and promotes the binding of the VEGF receptor 2 and the adherens junction molecules, VE-cadherin and beta-catenin, to the endothelial cytoskeleton. These changes are accompanied by the formation of a complex containing the VEGF receptor 2-VE-cadherin-beta-catenin. In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter. These results suggest that VEGF receptor 2 and the adherens junction act as shear-stress cotransducers, mediating the transduction of shear-stress signals into vascular endothelial cells.
Shay-Salit
Ayelet
A
Department of Anatomy and Cell Biology, Bruce Rappaport Research Institute and the Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
Shushy
Moran
M
Wolfovitz
Efrat
E
Yahav
Hava
H
Breviario
Ferruccio
F
Dejana
Elisabetta
E
Resnick
Nitzan
N
D021581:Active Transport, Cell Nucleus; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D018390:Gene Targeting; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor; D013314:Stress, Mechanical; D015534:Trans-Activators; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D015534:Trans-Activators; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D000099152:Cadherin 5