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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...

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Autores principales: Lampugnani, Maria Grazia, Zanetti, Adriana, Corada, Monica, Takahashi, Takamune, Balconi, Giovanna, Breviario, Ferruccio, Orsenigo, Fabrizio, Cattelino, Anna, Kemler, Rolf, Daniel, Thomas O., Dejana, Elisabetta
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
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.
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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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