SIGNALING AND REGULATION BY A MAMMALIAN GLUCOCORTICOID RECEPTOR IN DROSOPHILA CELLS

We demonstrate that the rat glucocorticoid receptor enhanced transcription in cultured Drosophila cells from Drosophila promoters linked to glucocorticoid response elements (GREs); promoters either containing or lacking a TATA box were rendered hormone inducible. Enhancement was dependent on the receptor, GREs, and the presence of an agonist ligand such as dexamethasone. The specific activities and relative efficacies of a series of potential ligands were generally similar in Drosophila and mammalian cells, except that dexamethasone mesylate, a potent antagonist in mammalian cells, was a strong agonist in Drosophila cells. A composite GRE, which mediates either positive or negative glucocorticoid regulation in animal cells depending on the presence and composition of the AP-1 transcription factor, conferred hormone-dependent enhancement, but not repression, in Drosophila cells. These results indicate that factors in addition to the receptor and GRE sequences participate as determinants of both signal transduction and transcriptional regulation by the glucocorticoid receptor, and that Drosophila cells carry functional homologs of many or all of those factors. Moreover, receptor activity can be exploited to obtain regulated gene expression in Drosophila.