Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor

EMBO J. 1987 Nov;6(11):3333-40.


We have detected nuclear localization signals within the 795 amino acid rat glucocorticoid receptor. Using a transient expression assay, we monitored by immunofluorescence the subcellular distribution of receptor derivatives and beta-galactosidase-receptor fusion proteins. Two distinct nuclear localization signals, NL1 and NL2, were defined. NL1 maps to a 28 amino acid segment closely associated, but not coincident with the DNA binding domain; NL2 resides within a 256 amino acid region that also includes the hormone binding domain. Most importantly, nuclear localization of fusion proteins containing either the full-length receptor or the NL2 region alone is fully hormone-dependent; similar results were obtained with the wild-type receptor, provided the analysis was performed in medium lacking serum and phenol red. The rate of hormone-induced nuclear localization of an NL2-containing fusion protein is consistent with the rapid kinetics of hormone-regulated transcription mediated by the receptor. Thus, hormonal control of nuclear localization contributes to the modulation of glucocorticoid receptor transcriptional regulatory activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Nucleus / metabolism*
  • Chromosome Deletion
  • Fluorescent Antibody Technique
  • Genes
  • Genetic Vectors
  • Mutation
  • Protein Sorting Signals / metabolism*
  • Rats
  • Receptors, Glucocorticoid / analysis
  • Receptors, Glucocorticoid / genetics*
  • Recombinant Fusion Proteins / analysis
  • beta-Galactosidase / analysis
  • beta-Galactosidase / genetics


  • Protein Sorting Signals
  • Receptors, Glucocorticoid
  • Recombinant Fusion Proteins
  • beta-Galactosidase