Early endosomal regulation of Smad-dependent signaling in endothelial cells

Απλή σελίδα τεκμηρίου
dc.contributor.authorPanopoulou, E.en
dc.contributor.authorGillooly, D. J.en
dc.contributor.authorWrana, J. L.en
dc.contributor.authorZerial, M.en
dc.contributor.authorStenmark, H.en
dc.contributor.authorMurphy, C.en
dc.contributor.authorFotsis, T.en
dc.date.accessioned2015-11-24T19:23:23Z
dc.date.available2015-11-24T19:23:23Z
dc.identifier.issn0021-9258-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/22294
dc.rightsDefault Licence-
dc.subjectAnimalsen
dc.subjectCarrier Proteins/physiologyen
dc.subjectCattleen
dc.subjectCells, Cultureden
dc.subjectDNA-Binding Proteins/*physiologyen
dc.subjectEndosomes/*physiologyen
dc.subjectEndothelium, Vascular/*physiologyen
dc.subjectKineticsen
dc.subjectPhosphorylationen
dc.subjectPromoter Regions, Geneticen
dc.subjectReceptors, Transforming Growth Factor beta/physiologyen
dc.subjectSignal Transduction/*physiologyen
dc.subjectSmad Proteinsen
dc.subjectTrans-Activators/*physiologyen
dc.subjectZinc Fingers/physiologyen
dc.subjectrab5 GTP-Binding Proteins/genetics/metabolismen
dc.titleEarly endosomal regulation of Smad-dependent signaling in endothelial cellsen
heal.abstractTransforming growth factor beta (TGFbeta) receptors require SARA for phosphorylation of the downstream transducing Smad proteins. SARA, a FYVE finger protein, binds to membrane lipids suggesting that activated receptors may interact with downstream signaling molecules at discrete endocytic locations. In the present study, we reveal a critical role for the early endocytic compartment in regulating Smad-dependent signaling. Not only is SARA localized on early endosomes, but also its minimal FYVE finger sequence is sufficient for early endosomal targeting. Expression of a SARA mutant protein lacking the FYVE finger inhibits downstream activin A signaling in endothelial cells. Moreover, a dominant-negative mutant of Rab5, a crucial protein for early endosome dynamics, causes phosphorylation and nuclear translocation of Smads leading to constitutive (i.e. ligand independent) transcriptional activation of a Smad-dependent promoter in endothelial cells. As inhibition of endocytosis using the K44A negative mutant of dynamin and RN-tre did not lead to activation of Smad-dependent transcription, the effects of the dominant-negative Rab5 are likely to be a consequence of altered membrane trafficking of constitutively formed TGFbeta/activin type I/II receptor complexes at the level of early endosomes. The results suggest an important interconnection between early endosomal dynamics and TGFbeta/activin signal transduction pathways.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1074/jbc.M107983200-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/11877415-
heal.identifier.secondaryhttp://www.jbc.org/content/277/20/18046.full.pdf-
heal.journalNameJ Biol Chemen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2002-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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