PMID- 10428027 OWN - NLM STAT- MEDLINE DCOM- 19990813 LR - 20220414 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 98 IP - 2 DP - 1999 Jul 23 TI - Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. PG - 147-57 AB - Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown. Here, targeted inactivation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdeltaC/deltaC) of the VE-cadherin gene was found not to affect assembly of endothelial cells in vascular plexi, but to impair their subsequent remodeling and maturation, causing lethality at 9.5 days of gestation. Deficiency or truncation of VE-cadherin induced endothelial apoptosis and abolished transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bcl2 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival. FAU - Carmeliet, P AU - Carmeliet P AD - Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium. peter.carmelilet@med.kuleuven.ac.be FAU - Lampugnani, M G AU - Lampugnani MG FAU - Moons, L AU - Moons L FAU - Breviario, F AU - Breviario F FAU - Compernolle, V AU - Compernolle V FAU - Bono, F AU - Bono F FAU - Balconi, G AU - Balconi G FAU - Spagnuolo, R AU - Spagnuolo R FAU - Oosthuyse, B AU - Oosthuyse B FAU - Dewerchin, M AU - Dewerchin M FAU - Zanetti, A AU - Zanetti A FAU - Angellilo, A AU - Angellilo A FAU - Mattot, V AU - Mattot V FAU - Nuyens, D AU - Nuyens D FAU - Lutgens, E AU - Lutgens E FAU - Clotman, F AU - Clotman F FAU - de Ruiter, M C AU - de Ruiter MC FAU - Gittenberger-de Groot, A AU - Gittenberger-de Groot A FAU - Poelmann, R AU - Poelmann R FAU - Lupu, F AU - Lupu F FAU - Herbert, J M AU - Herbert JM FAU - Collen, D AU - Collen D FAU - Dejana, E AU - Dejana E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Antigens, CD) RN - 0 (CTNNB1 protein, mouse) RN - 0 (Cadherins) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA Primers) RN - 0 (Endothelial Growth Factors) RN - 0 (Lymphokines) RN - 0 (Receptors, Growth Factor) RN - 0 (Trans-Activators) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - 0 (beta Catenin) RN - 0 (cadherin 5) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) SB - IM MH - Animals MH - Antigens, CD MH - Apoptosis/physiology MH - Cadherins/*genetics MH - Cell Survival/physiology MH - Cytoskeletal Proteins/physiology MH - Cytosol/chemistry/physiology MH - DNA Primers MH - Endothelial Growth Factors/*physiology MH - Endothelium, Vascular/chemistry/*cytology/ultrastructure MH - Fetus/cytology MH - Gene Expression Regulation, Developmental MH - Hematopoiesis/physiology MH - In Situ Nick-End Labeling MH - Intercellular Junctions/physiology MH - Lymphokines/*physiology MH - Mice MH - Mice, Transgenic MH - Microscopy, Electron MH - Mutagenesis, Site-Directed MH - Neovascularization, Physiologic/*physiology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Receptor Protein-Tyrosine Kinases/physiology MH - Receptors, Growth Factor/physiology MH - Receptors, Vascular Endothelial Growth Factor MH - Signal Transduction/physiology MH - *Trans-Activators MH - Vascular Endothelial Growth Factor A MH - Vascular Endothelial Growth Factors MH - beta Catenin EDAT- 1999/07/31 00:00 MHDA- 1999/07/31 00:01 CRDT- 1999/07/31 00:00 PHST- 1999/07/31 00:00 [pubmed] PHST- 1999/07/31 00:01 [medline] PHST- 1999/07/31 00:00 [entrez] AID - S0092-8674(00)81010-7 [pii] AID - 10.1016/s0092-8674(00)81010-7 [doi] PST - ppublish SO - Cell. 1999 Jul 23;98(2):147-57. doi: 10.1016/s0092-8674(00)81010-7.