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dc.contributor.authorKlingenberg, Olav
dc.contributor.authorWiedlocha, Antoni
dc.contributor.authorRapak, Andrzej
dc.contributor.authorMuñoz Martínez, Raquel 
dc.contributor.authorFalnes, Pål
dc.contributor.authorOlsnes, Sjur
dc.date.accessioned2020-06-08T12:13:19Z
dc.date.available2020-06-08T12:13:19Z
dc.date.issued1998
dc.identifier.citationJournal of Biological Chemistry, 1998, vol. 273, n. 18. p. 11164-11172es
dc.identifier.issn0021-9258es
dc.identifier.urihttp://uvadoc.uva.es/handle/10324/41004
dc.descriptionProducción Científicaes
dc.description.abstractAcidic fibroblast growth factor (aFGF) is a potent mitogen. It acts through activation of specific cell surface receptors leading to intracellular tyrosine phosphorylation cascades, but several reports also indicate that aFGF enters cells and that it has an intracellular function as well. The aFGF(K132E) mutant binds to and activates fibroblast growth factor receptors equally strongly as the wild-type, but it is a poor mitogen. We demonstrate that aFGF(K132E) enters NIH 3T3 cells and is transported to the nuclear fraction like wild-type aFGF. A fusion protein of aFGF(K132E) and diphtheria toxin A-fragment (aFGF(K132E)-DT-A) and a similar fusion protein containing wild-type aFGF (aFGF-DT-A) were reconstituted with diphtheria toxin B-fragment. Both fusion proteins were translocated to the cytosol by the diphtheria toxin pathway and subsequently recovered from the nuclear fraction. Whereas translocation of aFGF-DT-A stimulated DNA synthesis in U2OSDR1 cells lacking functional fibroblast growth factor receptors, aFGF(K132E)-DT-A did not. The mutation disrupts a protein kinase C phosphorylation site in the growth factor making it unable to be phosphorylated. The data indicate that a defect in the intracellular action of aFGF(K132E) is the reason for its strongly reduced mitogenicity, possibly due to inability to be phosphorylated.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/*
dc.subject.classificationDNA synthesises
dc.subject.classificationReplicación de ADNes
dc.titleInability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cellses
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 1998 American Society for Biochemistry and Molecular Biologyes
dc.identifier.doi10.1074/jbc.273.18.11164es
dc.relation.publisherversionhttps://www.jbc.org/content/273/18/11164es
dc.peerreviewedSIes
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Unported*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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