Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/41004
Título
Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cells
Autor
Año del Documento
1998
Editorial
American Society for Biochemistry and Molecular Biology
Descripción
Producción Científica
Documento Fuente
Journal of Biological Chemistry, 1998, vol. 273, n. 18. p. 11164-11172
Resumo
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.
Palabras Clave
DNA synthesis
Replicación de ADN
ISSN
0021-9258
Revisión por pares
SI
Version del Editor
Propietario de los Derechos
© 1998 American Society for Biochemistry and Molecular Biology
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
Aparece en las colecciones
Arquivos deste item
Exceto quando indicado o contrário, a licença deste item é descrito como Attribution-NonCommercial-NoDerivs 3.0 Unported