VEGF autoregulates its proliferative and migratory ERK1/2 and p38 cascades by enhancing the expression of DUSP1 and DUSP5 phosphatases in endothelial cells

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dc.contributor.authorBellou, S.en
dc.contributor.authorHink, M. A.en
dc.contributor.authorBagli, E.en
dc.contributor.authorPanopoulou, E.en
dc.contributor.authorBastiaens, P. I.en
dc.contributor.authorMurphy, C.en
dc.contributor.authorFotsis, T.en
dc.date.accessioned2015-11-24T18:50:52Z
dc.date.available2015-11-24T18:50:52Z
dc.identifier.issn1522-1563-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/18166
dc.rightsDefault Licence-
dc.subjectCell Movement/physiologyen
dc.subjectCell Nucleus/drug effects/metabolismen
dc.subjectCell Proliferationen
dc.subjectCells, Cultureden
dc.subjectDrug Interactionsen
dc.subjectDual Specificity Phosphatase 1/genetics/metabolismen
dc.subjectDual-Specificity Phosphatases/genetics/metabolismen
dc.subjectEndothelial Cells/*cytology/*enzymologyen
dc.subjectExtracellular Signal-Regulated MAP Kinases/*metabolismen
dc.subject*Homeostasisen
dc.subjectHumansen
dc.subjectMitogen-Activated Protein Kinase 1/metabolismen
dc.subjectMitogen-Activated Protein Kinase 3/metabolismen
dc.subjectMitogen-Activated Protein Kinase Phosphatases/*metabolismen
dc.subjectPhosphorylationen
dc.subjectTissue Distributionen
dc.subjectTranscription, Genetic/physiologyen
dc.subjectUmbilical Veins/cytologyen
dc.subjectUp-Regulation/physiologyen
dc.subjectVascular Endothelial Growth Factor A/*metabolism/pharmacologyen
dc.subjectp38 Mitogen-Activated Protein Kinases/metabolismen
dc.titleVEGF autoregulates its proliferative and migratory ERK1/2 and p38 cascades by enhancing the expression of DUSP1 and DUSP5 phosphatases in endothelial cellsen
heal.abstractVascular endothelial growth factor (VEGF) is a key angiogenic factor that regulates proliferation and migration of endothelial cells via phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2) and p38, respectively. Here, we demonstrate that VEGF strongly induces the transcription of two dual-specificity phosphatase (DUSP) genes DUSP1 and DUSP5 in endothelial cells. Using fluorescence microscopy, fluorescence lifetime imaging (FLIM), and fluorescence cross-correlation spectroscopy (FCCS), we found that DUSP1/mitogen-activated protein kinases phosphatase-1 (MKP-1) was localized in both the nucleus and cytoplasm of endothelial cells, where it existed in complex with p38 (effective dissociation constant, K(D)(eff), values of 294 and 197 nM, respectively), whereas DUSP5 was localized in the nucleus of endothelial cells in complex with ERK1/2 (K(D)(eff) 345 nM). VEGF administration affected differentially the K(D)(eff) values of the DUSP1/p38 and DUSP5/ERK1/2 complexes. Gain-of-function and lack-of-function approaches revealed that DUSP1/MKP-1 dephosphorylates primarily VEGF-phosphorylated p38, thereby inhibiting endothelial cell migration, whereas DUSP5 dephosphorylates VEGF-phosphorylated ERK1/2 inhibiting proliferation of endothelial cells. Moreover, DUSP5 exhibited considerable nuclear anchoring activity on ERK1/2 in the nucleus, thereby diminishing ERK1/2 export to the cytoplasm decreasing its further availability for activation.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1152/ajpcell.00058.2009-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/19741200-
heal.identifier.secondaryhttp://ajpcell.physiology.org/content/297/6/C1477.full.pdf-
heal.journalNameAm J Physiol Cell Physiolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2009-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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