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
Amino Acid Sequence
Animals
Binding Sites
Biological Transport/drug effects
Cell Nucleus/drug effects,metabolism
Cytoplasm/drug effects,enzymology,metabolism
DNA/genetics,metabolism
DNA-Binding Proteins/chemistry,genetics,metabolism
Dimerization
Gene Expression Regulation/drug effects
Ligands
MAP Kinase Signaling System/drug effects
Mutation
Nerve Growth Factor/pharmacology
Nuclear Localization Signals
Nuclear Receptor Subfamily 4, Group A, Member 1
PC12 Cells
Phosphorylation/drug effects
Phosphoserine/metabolism
Protein Structure, Tertiary
Rats
Receptor Cross-Talk/drug effects
Receptor Protein-Tyrosine Kinases/metabolism
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid/genetics,metabolism
Receptors, Steroid
Recombinant Fusion Proteins/genetics,metabolism
Retinoid X Receptors
Retinoids/pharmacology
Transcription Factors/chemistry,genetics,metabolism
ras Proteins/metabolism
Chemicals
DNA-Binding Proteins
Ligands
Nr4a1 protein, rat
Nuclear Localization Signals
Nuclear Receptor Subfamily 4, Group A, Member 1
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid
Receptors, Steroid
Recombinant Fusion Proteins
Retinoid X Receptors
Retinoids
Transcription Factors
Phosphoserine
DNA
Nerve Growth Factor
Receptor Protein-Tyrosine Kinases
ras Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Katagiri Y
Section on Growth Factors, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. katagiriy@usa.redcross.org
Takeda K
Yu Z X
Ferrans V J
Ozato K
Guroff G