| p120-Catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation. | |
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MedLine Citation:
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PMID: 18641366 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vascular endothelial-cadherin (VE-cad) is localized to adherens junctions at endothelial cell borders and forms a complex with alpha-, beta-, gamma-, and p120-catenins (p120). We previously showed that the VE-cad complex disassociates to form short-lived "gaps" during leukocyte transendothelial migration (TEM); however, whether these gaps are required for leukocyte TEM is not clear. Recently p120 has been shown to control VE-cad surface expression through endocytosis. We hypothesized that p120 regulates VE-cad surface expression, which would in turn have functional consequences for leukocyte transmigration. Here we show that endothelial cells transduced with an adenovirus expressing p120GFP fusion protein significantly increase VE-cad expression. Moreover, endothelial junctions with high p120GFP expression largely prevent VE-cad gap formation and neutrophil leukocyte TEM; if TEM occurs, the length of time required is prolonged. We find no evidence that VE-cad endocytosis plays a role in VE-cad gap formation and instead show that this process is regulated by changes in VE-cad phosphorylation. In fact, a nonphosphorylatable VE-cad mutant prevented TEM. In summary, our studies provide compelling evidence that VE-cad gap formation is required for leukocyte transmigration and identify p120 as a critical intracellular mediator of this process through its regulation of VE-cad expression at junctions. |
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Authors:
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Pilar Alcaide; Gail Newton; Scott Auerbach; Seema Sehrawat; Tanya N Mayadas; David E Golan; Patrick Yacono; Peter Vincent; Andrew Kowalczyk; Francis W Luscinskas |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-07-18 |
Journal Detail:
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Title: Blood Volume: 112 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-23 Completed Date: 2008-10-09 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2770-9 Citation Subset: AIM; IM |
Affiliation:
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Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism* Cadherins / metabolism* Catenins Cell Adhesion Molecules / metabolism* Cells, Cultured Chemotaxis, Leukocyte* Endocytosis Endothelial Cells / cytology, metabolism Endothelium / metabolism Gap Junctions / metabolism Green Fluorescent Proteins / metabolism Half-Life Humans Leukocytes / cytology*, metabolism* Phosphoproteins / metabolism* Phosphorylation Protein Binding Protein Transport Recombinant Fusion Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL077870/HL/NHLBI NIH HHS; HL32854/HL/NHLBI NIH HHS; HL36028/HL/NHLBI NIH HHS; P01 HL036028-230005/HL/NHLBI NIH HHS; P01 HL036028-239002/HL/NHLBI NIH HHS; R01 HL053993-13/HL/NHLBI NIH HHS; R01AR050501/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Cadherins; 0/Catenins; 0/Cell Adhesion Molecules; 0/Phosphoproteins; 0/Recombinant Fusion Proteins; 0/cadherin 5; 0/delta catenin; 147336-22-9/Green Fluorescent Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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