We created fusion chimeras between GR and other nuclear receptors that manifest ligand dependent cytoplasmic/nuclear translocation for the chimeric receptor in response to the heterologous ligand. The approach has been successfuly developed both for the retinoic acid receptor (RAR) and the estrogen receptor (ER). We developed cell lines which express fluorescently tagged versions of the receptor chimeras. The ER-GR chimeras have been utilized to screen chemical libraries, and identify new compounds with ER stimulating activity. Thus, the concept that chimeric GR fusions can be used to identify new ligands has been confirmed in a large scale screening protocol. We now believe that this approach can be generalized to many members of the nuclear receptor super-family, opening a new avenue for ligand discovery.
