Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B.
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.
Katagiri
Y
Y
Section on Growth Factors, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. katagiriy@usa.redcross.org
Takeda
K
K
Yu
Z X
ZX
Ferrans
V J
VJ
Ozato
K
K
Guroff
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects*; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology*; D019913:Nuclear Localization Signals; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D020239:Receptor Cross-Talk / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D008024:Ligands; C539820:Nr4a1 protein, rat; D019913:Nuclear Localization Signals; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D010768:Phosphoserine; D004247:DNA; D020932:Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins