Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells

Molecular Biology of the Cell
Estela CañónAna Aranda

Abstract

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 tr...Continue Reading

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Citations

Nov 23, 2006·Histochemistry and Cell Biology·Camillo Di GiulioAmelia Cataldi
Aug 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pawan GuptaLi-Na Wei
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Winyoo ChowanadisaiMark A Messerli
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