Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B

Nat Cell Biol. 2000 Jul;2(7):435-40. doi: 10.1038/35017072.

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
  • Cell Nucleus / metabolism*
  • Cytoplasm / drug effects
  • Cytoplasm / enzymology
  • Cytoplasm / metabolism
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / 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
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Steroid
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retinoid X Receptors
  • Retinoids / pharmacology*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • ras Proteins / metabolism

Substances

  • 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