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Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148
Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic endothelial cells differing for vascular endothelial cadherin (VE-cadherin) expression only, we found that the presence of this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199373/ https://www.ncbi.nlm.nih.gov/pubmed/12771128 http://dx.doi.org/10.1083/jcb.200209019 |
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author | Lampugnani, Maria Grazia Zanetti, Adriana Corada, Monica Takahashi, Takamune Balconi, Giovanna Breviario, Ferruccio Orsenigo, Fabrizio Cattelino, Anna Kemler, Rolf Daniel, Thomas O. Dejana, Elisabetta |
author_facet | Lampugnani, Maria Grazia Zanetti, Adriana Corada, Monica Takahashi, Takamune Balconi, Giovanna Breviario, Ferruccio Orsenigo, Fabrizio Cattelino, Anna Kemler, Rolf Daniel, Thomas O. Dejana, Elisabetta |
author_sort | Lampugnani, Maria Grazia |
collection | PubMed |
description | Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic endothelial cells differing for vascular endothelial cadherin (VE-cadherin) expression only, we found that the presence of this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation in tyrosine, p44/p42 MAP kinase phosphorylation, and cell proliferation. VE-cadherin truncated in β-catenin but not p120 binding domain is unable to associate with VEGFR-2 and to induce its inactivation. β-Catenin–null endothelial cells are not contact inhibited by VE-cadherin and are still responsive to VEGF, indicating that this protein is required to restrain growth factor signaling. A dominant-negative mutant of high cell density–enhanced PTP 1 (DEP-1)//CD148 as well as reduction of its expression by RNA interference partially restore VEGFR-2 phosphorylation and MAP kinase activation. Overall the data indicate that VE-cadherin–β-catenin complex participates in contact inhibition of VEGF signaling. Upon stimulation with VEGF, VEGFR-2 associates with the complex and concentrates at cell–cell contacts, where it may be inactivated by junctional phosphatases such as DEP-1. In sparse cells or in VE-cadherin–null cells, this phenomenon cannot occur and the receptor is fully activated by the growth factor. |
format | Text |
id | pubmed-2199373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21993732008-05-01 Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 Lampugnani, Maria Grazia Zanetti, Adriana Corada, Monica Takahashi, Takamune Balconi, Giovanna Breviario, Ferruccio Orsenigo, Fabrizio Cattelino, Anna Kemler, Rolf Daniel, Thomas O. Dejana, Elisabetta J Cell Biol Article Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic endothelial cells differing for vascular endothelial cadherin (VE-cadherin) expression only, we found that the presence of this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation in tyrosine, p44/p42 MAP kinase phosphorylation, and cell proliferation. VE-cadherin truncated in β-catenin but not p120 binding domain is unable to associate with VEGFR-2 and to induce its inactivation. β-Catenin–null endothelial cells are not contact inhibited by VE-cadherin and are still responsive to VEGF, indicating that this protein is required to restrain growth factor signaling. A dominant-negative mutant of high cell density–enhanced PTP 1 (DEP-1)//CD148 as well as reduction of its expression by RNA interference partially restore VEGFR-2 phosphorylation and MAP kinase activation. Overall the data indicate that VE-cadherin–β-catenin complex participates in contact inhibition of VEGF signaling. Upon stimulation with VEGF, VEGFR-2 associates with the complex and concentrates at cell–cell contacts, where it may be inactivated by junctional phosphatases such as DEP-1. In sparse cells or in VE-cadherin–null cells, this phenomenon cannot occur and the receptor is fully activated by the growth factor. The Rockefeller University Press 2003-05-26 /pmc/articles/PMC2199373/ /pubmed/12771128 http://dx.doi.org/10.1083/jcb.200209019 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Lampugnani, Maria Grazia Zanetti, Adriana Corada, Monica Takahashi, Takamune Balconi, Giovanna Breviario, Ferruccio Orsenigo, Fabrizio Cattelino, Anna Kemler, Rolf Daniel, Thomas O. Dejana, Elisabetta Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title | Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title_full | Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title_fullStr | Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title_full_unstemmed | Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title_short | Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148 |
title_sort | contact inhibition of vegf-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase dep-1/cd148 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199373/ https://www.ncbi.nlm.nih.gov/pubmed/12771128 http://dx.doi.org/10.1083/jcb.200209019 |
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