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首页> 外文期刊>Molecular biology of the cell >Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells
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Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells

机译：视黄酸对神经元细胞CREB和ERK磷酸化的快速作用

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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.
机译：维甲酸（RA）是神经元细胞分化的有效调节剂。 RA通常通过与核受体结合来激活基因表达，核受体与靶基因调节区域中的响应元件（RARE）相互作用。我们在这里显示，在类视黄醇引起神经突延伸的PC12细胞亚克隆中，RA诱导CREB（环状AMP响应元件结合蛋白）的快速持续磷酸化，与非基因组效应相容。 RA还引起大鼠胚胎的大脑皮层细胞和背根神经节神经元原代培养物中CREB磷酸化的快速增加。 RA介导的CREB磷酸化可直接刺激CREB依赖的转录活性，并激活诸如c-fos的基因表达，而c-fos在其启动子中不包含RARE，但包含cAMP响应元件（CRE）。 CREB是神经元细胞中细胞外信号调节激酶ERK1 / 2信号传导的主要目标，我们在这里证明RA诱导早期刺激ERK1 / 2，这是CREB磷酸化和转录活性所必需的。这些结果表明，RA通过非基因组机制刺激了导致转录因子磷酸化的信号通路，进而激活了神经元分化相关基因的转录。

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