Insertion of an amino acid in the DNA-binding domain of the glucocorticoidreceptor as a result of alternative splicing

When the human glucocorticoid receptor (GR) was first sequenced, a predomin ant form (GR alpha) and a minor variant (GR beta) were identified (1). In t he present communication, we describe a new variant of the glucocorticoid r eceptor (GR gamma) in which, as a result of alternative splicing, three bas es are retained from the intron separating exons 3 and 4. These three bases code for an additional amino acid (arginine) in the DNA binding domain of the receptor. Insertion of arginine at this site has previously been shown to decrease transcriptional activation by the GR to 48% that of GR alpha (2 ). Analysis of cDNA from different tissues shows that the novel form is wid ely expressed at a relatively high level (between 3.8 and 8.7% of total GR) .