English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124264
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Protein kinase D activity controls endothelial nitric oxide synthesis

AuthorsAicart-Ramos, Clara; Sánchez-Ruiloba, Lucía; Gómez-Parrizas, Mónica; Zaragoza, Carlos; Iglesias, Teresa ; Rodríguez-Crespo, Ignacio
Issue Date2014
PublisherCompany of Biologists
CitationJournal of Cell Science 127: 3360-3372 (2014)
AbstractVascular endothelial growth factor (VEGF) regulates key functions of the endothelium, such as angiogenesis or vessel repair in processes involving endothelial nitric oxide synthase (eNOS) activation. One of the effector kinases that become activated in endothelial cells upon VEGF treatment is protein kinase D (PKD). Here, we show that PKD phosphorylates eNOS, leading to its activation and a concomitant increase in NO synthesis. Using mass spectrometry, we show that the purified active kinase specifically phosphorylates recombinant eNOS on Ser1179. Treatment of endothelial cells with VEGF or phorbol 12,13-dibutyrate (PDBu) activates PKD and increases eNOS Ser1179 phosphorylation. In addition, pharmacological inhibition of PKD and gene silencing of both PKD1 and PKD2 abrogate VEGF signaling, resulting in a clear diminished migration of endothelial cells in a wound healing assay. Finally, inhibition of PKD in mice results in an almost complete disappearance of the VEGF-induced vasodilatation, as monitored through determination of the diameter of the carotid artery. Hence, our data indicate that PKD is a new regulatory kinase of eNOS in endothelial cells whose activity orchestrates mammalian vascular tone.
Publisher version (URL)http://dx.doi.org/10.1242/jcs.148601
URIhttp://hdl.handle.net/10261/124264
DOI10.1242/jcs.148601
Identifiersdoi: 10.1242/jcs.148601
issn: 0021-9533
e-issn: 1477-9137
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
Protein kinase D.pdf3,48 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.