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dc.creatorBruzzone, Ariana-
dc.creatorSaulière, Aude-
dc.creatorFinana, Frédéric-
dc.creatorSénard, Jean Michel-
dc.creatorLuthy, Isabel Alicia-
dc.creatorGalés, Céline-
dc.date2016-07-26T13:53:14Z-
dc.date2016-07-26T13:53:14Z-
dc.date2014-03-30-
dc.date2016-06-15T19:08:50Z-
dc.date.accessioned2019-04-29T15:47:04Z-
dc.date.available2019-04-29T15:47:04Z-
dc.date.issued2016-07-26T13:53:14Z-
dc.date.issued2016-07-26T13:53:14Z-
dc.date.issued2014-03-30-
dc.date.issued2016-06-15T19:08:50Z-
dc.identifierBruzzone, Ariana; Saulière, Aude; Finana, Frédéric ; Sénard, Jean Michel; Luthy, Isabel Alicia; et al.; Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals; Federation of American Societies for Experimental Biology; Faseb Journal; 28; 3; 30-3-2014; 1342-1354-
dc.identifier0892-6638-
dc.identifierhttp://hdl.handle.net/11336/6676-
dc.identifier1530-6860-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/301903-
dc.descriptionThe role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs.-
dc.descriptionFil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina-
dc.descriptionFil: Saulière, Aude. Inserm; Francia-
dc.descriptionFil: Finana, Frédéric . Institut de Recherche Pierre Fabre; Francia-
dc.descriptionFil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; Francia-
dc.descriptionFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina-
dc.descriptionFil: Galés, Céline. Inserm; Francia-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherFederation of American Societies for Experimental Biology-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.13-239285-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/28/3/1342.long-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1096/fj.13-239285-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectMCF-10A-
dc.subjectHUMAN BREAST CELL LINE-
dc.subjectEPAC-
dc.subjectPKA-
dc.subjectSIGNALING COMPARTMENTALIZATION-
dc.subjectBioquímica y Biología Molecular-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleDosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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