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Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis

2022-12Journal article Open access
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dc.contributor.authorJin, Yi
dc.contributor.authorDing, Yindi
dc.contributor.authorRichards, Mark
dc.contributor.authorKaakinen, Mika
dc.contributor.authorGiese, Wolfgang
dc.contributor.authorBaumann, Elisabeth
dc.contributor.authorSzymborska, Anna
dc.contributor.authorRosa, André
dc.contributor.authorNordling, Sofia
dc.contributor.authorSchimmel, Lilian
dc.contributor.authorAkmeriç, Emir Bora
dc.contributor.authorPena, Andreia
dc.contributor.authorNwadozi, Emmanuel
dc.contributor.authorJamalpour, Maria
dc.contributor.authorHolstein, Katrin
dc.contributor.authorSáinz-Jaspeado, Miguel
dc.contributor.authorBernabeu, Miguel O.
dc.contributor.authorWelsh, Michael
dc.contributor.authorGordon, Emma
dc.contributor.authorFranco, Claudio A.
dc.contributor.authorVestweber, Dietmar
dc.contributor.authorEklund, Lauri
dc.contributor.authorGerhardt, Holger
dc.contributor.authorClaesson-Welsh, Lena
dc.date.accessioned2023-10-11T09:03:08Z
dc.date.available2023-10-11T09:03:08Z
dc.date.issued2022-12
dc.description.abstractVascular 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/s44161-022-00172-zpt_PT
dc.identifier.eid85161153971
dc.identifier.issn2731-0590
dc.identifier.pmcPMC7615285
dc.identifier.pmid37936984
dc.identifier.urihttp://hdl.handle.net/10400.14/42831
dc.identifier.wos001124835500019
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleTyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1173pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage1156pt_PT
oaire.citation.titleNature Cardiovascular Researchpt_PT
oaire.citation.volume1pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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