DC Field | Value | Language |
---|---|---|
dc.contributor.author | Frye, Maike | ko |
dc.contributor.author | Dierkes, Martina | ko |
dc.contributor.author | Kueppers, Verena | ko |
dc.contributor.author | Vockel, Matthias | ko |
dc.contributor.author | Tomm, Janina | ko |
dc.contributor.author | Zeuschner, Dagmar | ko |
dc.contributor.author | Rossaint, Jan | ko |
dc.contributor.author | Zarbock, Alexander | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.contributor.author | Peters, Kevin | ko |
dc.contributor.author | Nottebaum, Astrid Fee | ko |
dc.contributor.author | Vestweber, Dietmar | ko |
dc.date.accessioned | 2016-06-07T09:10:37Z | - |
dc.date.available | 2016-06-07T09:10:37Z | - |
dc.date.created | 2016-02-12 | - |
dc.date.created | 2016-02-12 | - |
dc.date.created | 2016-02-12 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.citation | JOURNAL OF EXPERIMENTAL MEDICINE, v.212, no.13, pp.2267 - 2287 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10203/207793 | - |
dc.description.abstract | Vascular endothelial (VE)-protein tyrosine phosphatase (PTP) associates with VE-cadherin, thereby supporting its adhesive activity and endothelial junction integrity. VE-PTP also associates with Tie-2, dampening the tyrosine kinase activity of this receptor that can support stabilization of endothelial junctions. Here, we have analyzed how interference with VE-PTP affects the stability of endothelial junctions in vivo. Blocking VE-PTP by antibodies, a specific pharmacological inhibitor (AKB-9778), and gene ablation counteracted vascular leak induction by inflammatory mediators. In addition, leukocyte transmigration through the endothelial barrier was attenuated. Interference with Tie-2 expression in vivo reversed junction-stabilizing effects of AKB-9778 into junction-destabilizing effects. Furthermore, lack of Tie-2 was sufficient to weaken the vessel barrier. Mechanistically, inhibition of VE-PTP stabilized endothelial junctions via Tie-2, which triggered activation of Rap1, which then caused the dissolution of radial stress fibers via Rac1 and suppression of nonmuscle myosin II. Remarkably, VE-cadherin gene ablation did not abolish the junction-stabilizing effect of the VE-PTP inhibitor. Collectively, we conclude that inhibition of VE-PTP stabilizes challenged endothelial junctions in vivo via Tie-2 by a VE-cadherin-independent mechanism. In the absence of Tie-2, however, VE-PTP inhibition destabilizes endothelial barrier integrity in agreement with the VE-cadherin-supportive effect of VE-PTP | - |
dc.language | English | - |
dc.publisher | ROCKEFELLER UNIV PRESS | - |
dc.title | Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin | - |
dc.type | Article | - |
dc.identifier.wosid | 000368248500011 | - |
dc.identifier.scopusid | 2-s2.0-84961218854 | - |
dc.type.rims | ART | - |
dc.citation.volume | 212 | - |
dc.citation.issue | 13 | - |
dc.citation.beginningpage | 2267 | - |
dc.citation.endingpage | 2287 | - |
dc.citation.publicationname | JOURNAL OF EXPERIMENTAL MEDICINE | - |
dc.identifier.doi | 10.1084/jem.20150718 | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.nonIdAuthor | Frye, Maike | - |
dc.contributor.nonIdAuthor | Dierkes, Martina | - |
dc.contributor.nonIdAuthor | Kueppers, Verena | - |
dc.contributor.nonIdAuthor | Vockel, Matthias | - |
dc.contributor.nonIdAuthor | Tomm, Janina | - |
dc.contributor.nonIdAuthor | Zeuschner, Dagmar | - |
dc.contributor.nonIdAuthor | Rossaint, Jan | - |
dc.contributor.nonIdAuthor | Zarbock, Alexander | - |
dc.contributor.nonIdAuthor | Peters, Kevin | - |
dc.contributor.nonIdAuthor | Nottebaum, Astrid Fee | - |
dc.contributor.nonIdAuthor | Vestweber, Dietmar | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | PROTEIN-TYROSINE-PHOSPHATASE | - |
dc.subject.keywordPlus | INDUCED VASCULAR-PERMEABILITY | - |
dc.subject.keywordPlus | BLOOD-VESSEL DEVELOPMENT | - |
dc.subject.keywordPlus | CELL-JUNCTIONS | - |
dc.subject.keywordPlus | LEUKOCYTE EXTRAVASATION | - |
dc.subject.keywordPlus | BARRIER FUNCTION | - |
dc.subject.keywordPlus | VEGFR2 ACTIVITY | - |
dc.subject.keywordPlus | ANGIOPOIETIN-1 | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
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