VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF
- Nottebaum, Astrid F. Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Cagna, Giuseppe Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Winderlich, Mark Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Gamp, Alexander C. Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Linnepe, Ruth Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Polaschegg, Christian Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Filippova, Kristina Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Lyck, Ruth Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland
- Engelhardt, Britta Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland
- Kamenyeva, Olena Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Bixel, Maria Gabriele Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Butz, Stefan Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- Vestweber, Dietmar Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
- 2008-11-17
Published in:
- Journal of Experimental Medicine. - Rockefeller University Press. - 2008, vol. 205, no. 12, p. 2929-2945
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1084/jem.20080406
- ISSN 1540-9538
- Persistent URL
- https://sonar.ch/global/documents/60320
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