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oai:uvadoc.uva.es:10324/410042021-06-23T09:52:40Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Klingenberg, Olav Wiedlocha, Antoni Rapak, Andrzej Muñoz Martínez, Raquel Falnes, Pål Olsnes, Sjur 2020-06-08T12:13:19Z 2020-06-08T12:13:19Z 1998 Journal of Biological Chemistry, 1998, vol. 273, n. 18. p. 11164-11172 0021-9258 http://uvadoc.uva.es/handle/10324/41004 10.1074/jbc.273.18.11164 Producción Científica Acidic 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. application/pdf eng American Society for Biochemistry and Molecular Biology info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/3.0/ © 1998 American Society for Biochemistry and Molecular Biology Attribution-NonCommercial-NoDerivs 3.0 Unported DNA synthesis Replicación de ADN Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cells info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.jbc.org/content/273/18/11164 SI