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PMID: 15371543 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 15 ·No. 12 ·2004-12-00 ·Pages 5583-92

Cañón E, Cosgaya JM, Scsucova S, Aranda A

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 transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation.

MeSH Terms
Animals Cell Differentiation/drug effects Cell Proliferation/drug effects Cell Survival/drug effects Cells, Cultured Cyclic AMP/metabolism Cyclic AMP Response Element-Binding Protein/metabolism Gene Expression Regulation/drug effects Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism Neurons/cytology,drug effects,metabolism PC12 Cells Phosphorylation/drug effects Rats Response Elements/genetics Time Factors Transcription, Genetic/drug effects Tretinoin/pharmacology
Chemicals
Cyclic AMP Response Element-Binding Protein Tretinoin Cyclic AMP Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cañón Estela
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Cosgaya Jose Miguel
Scsucova Sona
Aranda Ana
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e04-05-0439
Published
2004-12-00
Epub
2004-00-15
Pages
5583-92
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC532036
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e04-05-0439 PMC Full Text View journal details
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