Biology:VE-cadherin
 Generic protein structure example |
Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 (Cluster of Differentiation 144), is a type of cadherin. It is encoded by the human gene CDH5.[1]
Function
VE-cadherin is a classical cadherin from the cadherin superfamily and the gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classic cadherin by imparting to cells the ability to adhere in a homophilic manner, the protein may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions.[2]
Integrity of intercellular junctions is a major determinant of permeability of the endothelium, and the VE-cadherin-based adherens junction is thought to be particularly important. VE-cadherin is known to be required for maintaining a restrictive endothelial barrier – early studies using blocking antibodies to VE-cadherin increased monolayer permeability in cultured cells[3] and resulted in interstitial edema and hemorrhage in vivo.[4] A recent study has shown that TNFAIP3 (A20, a dual-ubiquitin editing enzyme) is essential for stability and expression of VE-cadherin. Deubiquitinase function of A20 was shown to remove ubiquitin chains from VE-cadherin, thereby prevented loss of VE-cadherin expression at the endothelial adherens junctions.[5]
VE-cadherin is indispensable for proper vascular development – there have been two transgenic mouse models of VE-cadherin deficiency, both embryonic lethal due to vascular defects.[6][7] Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin.[8] Therefore, it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.
Interactions
VE-cadherin has been shown to interact with:
- Beta-catenin[9][10]
- Plakoglobin[9][10]
- PTPRB[11]
- Catenin (cadherin-associated protein), alpha 1[9][10]
- CTNND1[12][13]
- PTPmu (PTPRM)[14]
- PTPrho (PTPRT)[15]
As a biomarker
VE-cadherin may serve as a biomarker for radiation exposure.[16]
See also
References
- ↑ "Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue". Cell Regul. 2 (4): 261–70. April 1991. doi:10.1091/mbc.2.4.261. PMID 2059658.
- ↑ "Entrez Gene: CDH5 cadherin 5, type 2, VE-cadherin (vascular epithelium)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1003.
- ↑ "Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability". Blood 97 (6): 1679–84. March 2001. doi:10.1182/blood.V97.6.1679. PMID 11238107.
- ↑ "A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability". Blood 100 (3): 905–11. August 2002. doi:10.1182/blood.V100.3.905. PMID 12130501.
- ↑ "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery 4 (60): 60. May 2018. doi:10.1038/s41420-018-0056-3. PMID 29796309.
- ↑ "Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis". Cell 98 (2): 147–57. July 1999. doi:10.1016/S0092-8674(00)81010-7. PMID 10428027.
- ↑ "Role of vascular endothelial-cadherin in vascular morphogenesis". Development 126 (10): 2093–102. May 1999. doi:10.1242/dev.126.10.2093. PMID 10207135. http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=10207135.
- ↑ "VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly". Blood 105 (7): 2771–6. April 2005. doi:10.1182/blood-2004-06-2244. PMID 15604224.
- ↑ 9.0 9.1 9.2 "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res. 237 (2): 347–56. Dec 1997. doi:10.1006/excr.1997.3799. PMID 9434630.
- ↑ 10.0 10.1 10.2 "Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin". Am. J. Physiol. Lung Cell Mol. Physiol. 282 (6): L1330–8. Jun 2002. doi:10.1152/ajplung.00329.2001. PMID 12003790. http://ajplung.physiology.org/content/282/6/L1330.abstract.
- ↑ "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". EMBO J. 21 (18): 4885–95. Sep 2002. doi:10.1093/emboj/cdf497. PMID 12234928.
- ↑ "An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation". Exp. Cell Res. 274 (1): 35–44. Mar 2002. doi:10.1006/excr.2001.5436. PMID 11855855.
- ↑ "Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells". J. Cell Sci. 110 (17): 2065–77. Sep 1997. doi:10.1242/jcs.110.17.2065. PMID 9378757.
- ↑ "Receptor protein tyrosine phosphatase micro regulates the paracellular pathway in human lung microvascular endothelia.". Am J Pathol 166 (4): 1247–58. 2005. doi:10.1016/s0002-9440(10)62343-7. PMID 15793303.
- ↑ "Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).". Brain Res 1116 (1): 50–7. 2006. doi:10.1016/j.brainres.2006.07.122. PMID 16973135.
- ↑ "Soluble Vascular Endothelial Cadherin as a New Biomarker of Irradiation in Highly Irradiated Baboons with Bone Marrow Protection". Health Physics 110 (6): 598–605. June 2016. doi:10.1097/HP.0000000000000481. PMID 27115227.
Further reading
- "A novel endothelial-specific membrane protein is a marker of cell-cell contacts". J. Cell Biol. 118 (6): 1511–22. 1992. doi:10.1083/jcb.118.6.1511. PMID 1522121.
- "Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue". Cell Regul. 2 (4): 261–70. 1991. doi:10.1091/mbc.2.4.261. PMID 2059658.
- "Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin". Arterioscler. Thromb. Vasc. Biol. 15 (8): 1229–39. 1995. doi:10.1161/01.ATV.15.8.1229. PMID 7627717.
- "Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion". Microcirculation 4 (2): 267–77. 1997. doi:10.3109/10739689709146790. PMID 9219219.
- "Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells". J. Cell Sci. 110 (17): 2065–77. 1997. doi:10.1242/jcs.110.17.2065. PMID 9378757.
- "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res. 237 (2): 347–56. 1998. doi:10.1006/excr.1997.3799. PMID 9434630.
- "Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity". Genomics 49 (3): 467–71. 1998. doi:10.1006/geno.1998.5281. PMID 9615235.
- "VE-cadherin and desmoplakin are assembled into dermal microvascular endothelial intercellular junctions: a pivotal role for plakoglobin in the recruitment of desmoplakin to intercellular junctions". J. Cell Sci. 111 (20): 3045–57. 1998. doi:10.1242/jcs.111.20.3045. PMID 9739078.
- "An immunohistochemical study of cadherin 5 (VE-cadherin) in vascular endothelial cells in placentas with gestosis". J. Obstet. Gynaecol. Res. 24 (6): 375–84. 1999. doi:10.1111/j.1447-0756.1998.tb00112.x. PMID 10063232.
- "Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis". Cell 98 (2): 147–57. 1999. doi:10.1016/S0092-8674(00)81010-7. PMID 10428027.
- "SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin". J. Biol. Chem. 275 (8): 5983–6. 2000. doi:10.1074/jbc.275.8.5983. PMID 10681592.
- "Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins". Biochem. J. 349 (Pt 1): 159–67. 2001. doi:10.1042/0264-6021:3490159. PMID 10861224.
- "Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium". J. Immunol. 167 (4): 2323–30. 2001. doi:10.4049/jimmunol.167.4.2323. PMID 11490021.
- "Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin". J. Immunol. 168 (2): 588–96. 2002. doi:10.4049/jimmunol.168.2.588. PMID 11777950.
- "An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation". Exp. Cell Res. 274 (1): 35–44. 2002. doi:10.1006/excr.2001.5436. PMID 11855855.
- "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". Biochemistry 41 (12): 4107–16. 2002. doi:10.1021/bi0160314. PMID 11900554.
- "Antiphospholid antibodies regulate the expression of trophoblast cell adhesion molecules". Fertil. Steril. 77 (4): 805–11. 2003. doi:10.1016/S0015-0282(01)03258-7. PMID 11937138.
- "Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling". Arterioscler. Thromb. Vasc. Biol. 22 (4): 617–22. 2002. doi:10.1161/01.ATV.0000012268.84961.AD. PMID 11950700.
- "VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam". Mol. Biol. Cell 13 (4): 1175–89. 2002. doi:10.1091/mbc.01-07-0368. PMID 11950930.
- "VE-cadherin: adhesion at arm's length". Am J Physiol Cell Physiol 286 (5): C987–97. 2004. doi:10.1152/ajpcell.00522.2003. PMID 15075197.
External links
- VE-cadherin+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- CDH5 human gene location in the UCSC Genome Browser.
- CDH5 human gene details in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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