Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.14/42831 |
Resumo: | Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity. |
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Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosisVascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity.Veritati - Repositório Institucional da Universidade Católica PortuguesaJin, YiDing, YindiRichards, MarkKaakinen, MikaGiese, WolfgangBaumann, ElisabethSzymborska, AnnaRosa, AndréNordling, SofiaSchimmel, LilianAkmeriç, Emir BoraPena, AndreiaNwadozi, EmmanuelJamalpour, MariaHolstein, KatrinSáinz-Jaspeado, MiguelBernabeu, Miguel O.Welsh, MichaelGordon, EmmaFranco, Claudio A.Vestweber, DietmarEklund, LauriGerhardt, HolgerClaesson-Welsh, Lena2023-10-11T09:03:08Z2022-122022-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/42831eng2731-059010.1038/s44161-022-00172-z85161153971PMC761528537936984info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-09T01:37:07Zoai:repositorio.ucp.pt:10400.14/42831Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:35:48.654268Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
title |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
spellingShingle |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis Jin, Yi |
title_short |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
title_full |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
title_fullStr |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
title_full_unstemmed |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
title_sort |
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis |
author |
Jin, Yi |
author_facet |
Jin, Yi Ding, Yindi Richards, Mark Kaakinen, Mika Giese, Wolfgang Baumann, Elisabeth Szymborska, Anna Rosa, André Nordling, Sofia Schimmel, Lilian Akmeriç, Emir Bora Pena, Andreia Nwadozi, Emmanuel Jamalpour, Maria Holstein, Katrin Sáinz-Jaspeado, Miguel Bernabeu, Miguel O. Welsh, Michael Gordon, Emma Franco, Claudio A. Vestweber, Dietmar Eklund, Lauri Gerhardt, Holger Claesson-Welsh, Lena |
author_role |
author |
author2 |
Ding, Yindi Richards, Mark Kaakinen, Mika Giese, Wolfgang Baumann, Elisabeth Szymborska, Anna Rosa, André Nordling, Sofia Schimmel, Lilian Akmeriç, Emir Bora Pena, Andreia Nwadozi, Emmanuel Jamalpour, Maria Holstein, Katrin Sáinz-Jaspeado, Miguel Bernabeu, Miguel O. Welsh, Michael Gordon, Emma Franco, Claudio A. Vestweber, Dietmar Eklund, Lauri Gerhardt, Holger Claesson-Welsh, Lena |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Veritati - Repositório Institucional da Universidade Católica Portuguesa |
dc.contributor.author.fl_str_mv |
Jin, Yi Ding, Yindi Richards, Mark Kaakinen, Mika Giese, Wolfgang Baumann, Elisabeth Szymborska, Anna Rosa, André Nordling, Sofia Schimmel, Lilian Akmeriç, Emir Bora Pena, Andreia Nwadozi, Emmanuel Jamalpour, Maria Holstein, Katrin Sáinz-Jaspeado, Miguel Bernabeu, Miguel O. Welsh, Michael Gordon, Emma Franco, Claudio A. Vestweber, Dietmar Eklund, Lauri Gerhardt, Holger Claesson-Welsh, Lena |
description |
Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12 2022-12-01T00:00:00Z 2023-10-11T09:03:08Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.14/42831 |
url |
http://hdl.handle.net/10400.14/42831 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2731-0590 10.1038/s44161-022-00172-z 85161153971 PMC7615285 37936984 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133621737488384 |