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

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Abstract
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.