Disease relevance of CDH5

• METHODS AND RESULTS: Seven epithelioid sarcomas were immunostained by a polyclonal antibody that detects all cadherin subtypes and by monoclonal antibodies that detect epithelial cadherin (E-cadherin) and vascular-endothelial cadherin (VE cadherin) [1].
• A recombinant VE-cadherin cytoplasmic domain (rVE-cad CPD) was expressed in E. coli and purified through Ni-NTA spin columns [2].
• Assessing microvessels and angiogenesis in human breast cancer, using VE-cadherin [3].
• Both VE-cadherin and PECAM-1 had significantly reduced expression in lobular compared with ductal carcinomas: there was no difference with factor VIII [3].
• CONCLUSION: Increased secretion of VE-cadherin from the epicardial arteries is associated with the degree of coronary atherosclerosis, indicating the presence of atherosclerosis rather than disease activity [4].

High impact information on CDH5

• 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 [5].
• Our findings conclude that the interplay of fibrin fragments, leukocytes and VE-cadherin contribute to the pathogenesis of myocardial damage and reperfusion injury [6].
• Here, we identify a subpopulation of primitive endothelial-like cells derived from human embryonic stem cells (hESCs) that express PECAM-1, Flk-1, and VE-cadherin, but not CD45 (CD45negPFV cells), and that are uniquely responsible for endothelial and hematopoietic development [7].
• Together, through modulation of endothelial contractility and VE-cadherin-mediated adhesion, JAM-C helps to regulate vascular permeability and pathologic angiogenesis [8].
• Both biochemical and indirect immunofluorescence analyses of the adherens junction zone of EC monolayers revealed that neutrophil adhesion, not transmigration, induced disruption of the VE-cadherin complex and loss of its lateral junction localization [9].

Chemical compound and disease context of CDH5

• Inhibition of Rho by prolonged treatment of cells with C3 exoenzyme (Clostridium botulinum) eliminates actin stress fibers without disrupting the continuity of VE-cadherin staining, indicating that Rho-dependent stress fibers are not required for maintaining this adhesion receptor at sites of intercellular contact [10].
• Paracrine VEGF/VE-Cadherin Action on Ovarian Cancer Permeability [11].

Biological context of CDH5

• Thus, we investigated the effect of Rap1 on permeability and the VE-cadherin-mediated cell adhesion by expressing either constitutive active Rap1 or Rap1GAPII [12].
• Thrombin treatment of human umbilical vein endothelial cells promotes SHP2 tyrosine phosphorylation and dissociation from VE-cadherin complexes [13].
• One of the major goals in this study was to assess the differential gene expression of p120(ctn), Kaiso, and VE-cadherin in HCAEC at specific locations along the wound border to further our understanding of the molecular mechanisms involved in wound closure [14].
• VE-cadherin can interact with p120 catenin (p120(ctn)) to mediate cell locomotion and proliferation [14].
• Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migration from a confluent monolayer [15].

Anatomical context of CDH5

• SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin [13].
• However, interaction of VE-cadherin with the cytoskeleton is necessary to provide strength and cohesion to the junction [15].
• In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain [15].
• Thus, non-junctional VE-cadherin actively participates in inside-out signaling at the plasma membrane, leading to the development of endothelial membrane protrusions [16].
• VE-cadherin also appears to be required for cell-cell association, but additionally appears to play some role in the process of vacuolization or vacuole fusion leading to intercellular lumen formation [17].

Associations of CDH5 with chemical compounds

• The internalized VE-cadherin co-localized with early endosomes, and the lysosomal inhibitor chloroquine dramatically inhibited the down-regulation of VE-cadherin in cells expressing the IL-2R-VE-cadcyto mutant [18].
• This inhibitory effect of resveratrol reflected on the retention of VE-cadherin at cell-cell contacts as demonstrated by immunofluorescence [19].
• Detergent extraction of cells with Triton X-100 indicted that the majority of VE-cadherin and beta-catenin was Triton soluble, indicating that they are only weakly associated with the actin-based cytoskeleton [20].
• Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: mapping of the receptor-binding site in the NH2-terminal portions of the fibrin beta chains [21].
• Loss of cell adhesion, as well as N- and VE-cadherin and integrin beta1 cleavage, could be inhibited or significantly delayed by preincubation of P. gingivalis W83 gingipain-active extracellular extracts with the cysteine protease inhibitor Nalpha-p-tosyl-l-lysine chloromethylketone [22].
• Our results demonstrate that engagement of ICAM-1 by leukocytes results in tyrosine phosphorylation of VE-cadherin, which is required for efficient neutrophil TEM [23].
• In an in vitro Src assay, the VE-cadherin cytoplasmic domain is directly phosphorylated by purified Src as well as the tyrosine residue 685 (Tyr)685-containing peptide RPSLY(685)AQVQ [24].

Physical interactions of CDH5

• Deletion analysis using the yeast two-hybrid system revealed that the armadillo repeat domain of p0071 bound directly to VE-cadherin [25].
• We demonstrate that the nonreceptor protein-tyrosine phosphatase SHP2 co-precipitates with VE-cadherin complexes in confluent, quiescent human umbilical vein endothelial cells [13].
• These data suggest that desmoplakin may participate in the molecular organization of interendothelial junctions by interacting with VE-cadherin and promoting vimentin anchorage [26].
• Chloroquine treatment also resulted in the accumulation of a VE-cadherin fragment lacking the beta-catenin binding domain of the VE-cadherin cytoplasmic tail [18].
• Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state [27].

Co-localisations of CDH5

• METHODS AND RESULTS: Confocal microscopy analysis shows that IQGAP1 colocalizes with VE-cadherin at cell-cell contacts in unstimulated human endothelial cells (ECs) [28].
• Vascular endothelial cadherin (VE-cadherin) clusters were co-localized with beta-catenin, an important signal transduction ligand, and with alpha-catenin, which is thought to link the complex to the peri-junctional actin [29].

Regulatory relationships of CDH5

• In conclusion, cAMP-Epac-Rap1 signaling promotes decreased cell permeability by enhancing VE-cadherin-mediated adhesion lined by the rearranged cortical actin [12].
• VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells [16].
• PP2 also blocked TNF-alpha-induced tyrosine phosphorylation of VE-cadherin, gamma-catenin, and p120(ctn) [30].
• VE-cadherin expression levels are regulated by p120 catenin, which prevents lysosomal degradation of cadherins by unknown mechanisms [31].
• Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells [32].

Other interactions of CDH5

• In contrast to VE-cadherin, desmoplakin was found to associate with the non-armadillo head domain of p0071 [25].
• RESULTS: In VE cadherin transfectants, beta-catenin was targeted to junctional regions and the F-actin-based cytoskeleton formed parallel bundles reaching from one cell border to the other [33].
• The expression of VE-cadherin by the majority of cases, in the absence of E-cadherin, is consistent with an element of mesenchymal differentiation, possibly endothelial or perineurial [1].
• Therefore, the occurrence, distribution and hormonal control of the adherens junction protein vascular endothelial cadherin (VE-cadherin) and the tight junction proteins occludin and claudin in the human corpus luteum (CL) were investigated [34].
• Claudin 5 and VE-cadherin were only present in endothelial cells [34].

Analytical, diagnostic and therapeutic context of CDH5

• Detection of p120(ctn), Kaiso, and VE-cadherin mRNA was carried out using quantitative real time PCR [14].
• During capillary tube formation, Western blot and RT-PCR analysis revealed no marked change in VE-cadherin expression [35].
• Immunofluorescence, laser confocal microscopy, and Western immunobloting were used to assess VE cadherin distribution [36].
• Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models [37].
• Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall [38].

References