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VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation

Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endotheliu...

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Autores principales: Hayashi, Makoto, Majumdar, Arindam, Li, Xiujuan, Adler, Jeremy, Sun, Zuyue, Vertuani, Simona, Hellberg, Carina, Mellberg, Sofie, Koch, Sina, Dimberg, Anna, Young Koh, Gou, Dejana, Elisabetta, Belting, Heinz-Georg, Affolter, Markus, Thurston, Gavin, Holmgren, Lars, Vestweber, Dietmar, Claesson-Welsh, Lena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644080/
https://www.ncbi.nlm.nih.gov/pubmed/23575676
http://dx.doi.org/10.1038/ncomms2683
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author Hayashi, Makoto
Majumdar, Arindam
Li, Xiujuan
Adler, Jeremy
Sun, Zuyue
Vertuani, Simona
Hellberg, Carina
Mellberg, Sofie
Koch, Sina
Dimberg, Anna
Young Koh, Gou
Dejana, Elisabetta
Belting, Heinz-Georg
Affolter, Markus
Thurston, Gavin
Holmgren, Lars
Vestweber, Dietmar
Claesson-Welsh, Lena
author_facet Hayashi, Makoto
Majumdar, Arindam
Li, Xiujuan
Adler, Jeremy
Sun, Zuyue
Vertuani, Simona
Hellberg, Carina
Mellberg, Sofie
Koch, Sina
Dimberg, Anna
Young Koh, Gou
Dejana, Elisabetta
Belting, Heinz-Georg
Affolter, Markus
Thurston, Gavin
Holmgren, Lars
Vestweber, Dietmar
Claesson-Welsh, Lena
author_sort Hayashi, Makoto
collection PubMed
description Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp(−/−) teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation.
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spelling pubmed-36440802013-05-17 VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation Hayashi, Makoto Majumdar, Arindam Li, Xiujuan Adler, Jeremy Sun, Zuyue Vertuani, Simona Hellberg, Carina Mellberg, Sofie Koch, Sina Dimberg, Anna Young Koh, Gou Dejana, Elisabetta Belting, Heinz-Georg Affolter, Markus Thurston, Gavin Holmgren, Lars Vestweber, Dietmar Claesson-Welsh, Lena Nat Commun Article Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp(−/−) teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation. Nature Pub. Group 2013-04-09 /pmc/articles/PMC3644080/ /pubmed/23575676 http://dx.doi.org/10.1038/ncomms2683 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Hayashi, Makoto
Majumdar, Arindam
Li, Xiujuan
Adler, Jeremy
Sun, Zuyue
Vertuani, Simona
Hellberg, Carina
Mellberg, Sofie
Koch, Sina
Dimberg, Anna
Young Koh, Gou
Dejana, Elisabetta
Belting, Heinz-Georg
Affolter, Markus
Thurston, Gavin
Holmgren, Lars
Vestweber, Dietmar
Claesson-Welsh, Lena
VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title_full VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title_fullStr VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title_full_unstemmed VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title_short VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
title_sort ve-ptp regulates vegfr2 activity in stalk cells to establish endothelial cell polarity and lumen formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644080/
https://www.ncbi.nlm.nih.gov/pubmed/23575676
http://dx.doi.org/10.1038/ncomms2683
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