Abstract
The retinoid-X receptor (RXR) regulates multiple hormonal pathways through heterodimerization with nuclear receptors such as the all-trans retinoic acid receptor (RAR). The orphan nuclear receptor NGFI-B (also called Nur77) can heterodimerize with RXR. Here we show that nerve growth factor (NGF) induces the phosphorylation of Ser 105 of NGFI-B in PC12 phaeochromocytoma cells, resulting in translocation of the NGFI-B-RXR heterodimer complex out of the nucleus using nuclear export signals within NGFI-B. As a consequence of the redistribution of RXR, the transcriptional activity of RXR-RAR is reduced. NGFI-B-mediated nuclear export of receptors may serve as a mechanism for crosstalk between NGF and retinoid pathways.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Biological Transport / drug effects
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism*
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Cytoplasm / drug effects
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Cytoplasm / enzymology
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Cytoplasm / metabolism
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Gene Expression Regulation / drug effects*
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Ligands
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MAP Kinase Signaling System / drug effects*
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Mutation
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Nerve Growth Factor / pharmacology*
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Nuclear Localization Signals
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Nuclear Receptor Subfamily 4, Group A, Member 1
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PC12 Cells
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Phosphorylation / drug effects
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Phosphoserine / metabolism
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Protein Structure, Tertiary
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Rats
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Receptor Cross-Talk / drug effects
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism
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Receptors, Steroid
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Retinoid X Receptors
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Retinoids / pharmacology*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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ras Proteins / metabolism
Substances
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DNA-Binding Proteins
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Ligands
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Nr4a1 protein, rat
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Nuclear Localization Signals
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Steroid
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Recombinant Fusion Proteins
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Retinoid X Receptors
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Retinoids
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Transcription Factors
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Phosphoserine
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DNA
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Nerve Growth Factor
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Receptor Protein-Tyrosine Kinases
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ras Proteins