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Título : Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells
Autor : Cañón, Estela ; Cosgaya, José Miguel ; Scsucova, Sona; Aranda, Ana
Fecha de publicación : dic-2004
Editor: American Society for Cell Biology
Citación : Molecular Biology of the Cell 15(12): 5583–5592 (2004)
Resumen: Retinoic acid (RA) is a potent regulator of neuronal cell differentiation. RA normally activates gene expression by binding to nuclear receptors that interact with response elements (RAREs) in regulatory regions of target genes. We show here that in PC12 cell subclones in which the retinoid causes neurite extension, RA induces a rapid and sustained phosphorylation of CREB (cyclic AMP response element binding protein), compatible with a nongenomic effect. RA also causes a rapid increase of CREB phosphorylation in primary cultures of cerebrocortical cells and of dorsal root ganglia neurons from rat embryos. RA-mediated phosphorylation of CREB leads to a direct stimulation of CREB-dependent transcriptional activity and to activation of the expression of genes such as c-fos, which do not contain RAREs but contain cAMP response elements (CREs) in their promoters. CREB is a major target of extracellular signal regulated kinase ERK1/2 signaling in neuronal cells, and we demonstrate here that RA induces an early stimulation of ERK1/2, which is required both for CREB phosphorylation and transcriptional activity. These results demonstrate that RA, by a nongenomic mechanism, stimulates signaling pathways that lead to phosphorylation of transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation.
Descripción : Copyright © by American Society for Cell Biology.-- Final full-text version of the paper available at: http://www.molbiolcell.org/content/vol15/issue12/
Versión del editor: http://dx.doi.org/10.1091/mbc.E04-05-0439
URI : http://hdl.handle.net/10261/5349
DOI: 10.1091/mbc.E04-05-0439
ISSN: 1059-1524
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