Biosynthesis and expression of VE-cadherin is regulated by the PI3K/mTOR signaling pathway.
Vascular endothelial (VE)-cadherin is an essential protein of adherens junctions of endothelial cells and plays a pivotal role in vascular homeostasis. Mammalian target of rapamycin complex 2 (mTORC2) deficient mice display defects in fetal vascular development. Blocking mTOR or the upstream kinase phosphoinositide 3-kinase (PI3K) led to a dose-dependently decrease of the VE-cadherin mRNA and protein expression. Immunofluorescent staining showed a strongly decreased expression of VE-cadherin at the interface of human umbilical endothelial cells (HUVECs) followed by intercellular gap formation. Herewith, we demonstrated that the expression of VE-cadherin is dependent on mTOR and PI3K signaling.
Bieri
Michael
M
Laboratory for Heart Transplantation Immunology, Cardiology, Swiss Cardiovascular Center, University Hospital (Inselspital), CH-3010 Bern, Switzerland.
Oroszlan
Melinda
M
Zuppinger
Christian
C
Mohacsi
Paul J
PJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D000099152:Cadherin 5; C546842:MTOR protein, human; C546843:mTOR protein, mouse