VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF
| Autor: | Maria Gabriele Bixel, Stefan Butz, Giuseppe Cagna, Ruth Lyck, Astrid F. Nottebaum, Britta Engelhardt, Ruth Linnepe, Mark Winderlich, Alexander C. Gamp, Kristina Filippova, Dietmar Vestweber, Olena Kamenyeva, Christian Polaschegg |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
animal structures Endothelium Neutrophils Immunology Plakoglobin Endosomes Biology Vascular endothelial growth inhibitor environment and public health Article Cell Line Mice chemistry.chemical_compound Antigens CD Leukocytes medicine Animals Humans Immunology and Allergy Lymphocytes RNA Small Interfering beta Catenin Tumor Necrosis Factor-alpha Receptor-Like Protein Tyrosine Phosphatases Class 3 Endothelial Cells Articles Cadherins Cell biology Vascular endothelial growth factor B Vascular endothelial growth factor Endothelial stem cell enzymes and coenzymes (carbohydrates) Vascular endothelial growth factor A Intercellular Junctions medicine.anatomical_structure Vascular endothelial growth factor C chemistry gamma Catenin Cell Adhesion Molecules |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20080406 |
| Popis: | We have shown recently that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial-specific membrane protein, associates with vascular endothelial (VE)–cadherin and enhances VE-cadherin function in transfected cells (Nawroth, R., G. Poell, A. Ranft, U. Samulowitz, G. Fachinger, M. Golding, D.T. Shima, U. Deutsch, and D. Vestweber. 2002. EMBO J. 21:4885–4895). We show that VE-PTP is indeed required for endothelial cell contact integrity, because down-regulation of its expression enhanced endothelial cell permeability, augmented leukocyte transmigration, and inhibited VE-cadherin–mediated adhesion. Binding of neutrophils as well as lymphocytes to endothelial cells triggered rapid (5 min) dissociation of VE-PTP from VE-cadherin. This dissociation was only seen with tumor necrosis factor α–activated, but not resting, endothelial cells. Besides leukocytes, vascular endothelial growth factor also rapidly dissociated VE-PTP from VE-cadherin, indicative of a more general role of VE-PTP in the regulation of endothelial cell contacts. Dissociation of VE-PTP and VE-cadherin in endothelial cells was accompanied by tyrosine phoshorylation of VE-cadherin, β-catenin, and plakoglobin. Surprisingly, only plakoglobin but not β-catenin was necessary for VE-PTP to support VE-cadherin adhesion in endothelial cells. In addition, inhibiting the expression of VE-PTP preferentially increased tyrosine phosphorylation of plakoglobin but not β-catenin. In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not β-catenin. |
| Databáze: | OpenAIRE |
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