The present invention provides universal G protein-coupled receptor (GPCR) reporter constructs. The constructs comprise a serum response element, a cAMP response element, and a multiple response element. These reporter constructs are able to detect activities of all GPCRs examined. Further provided by the present invention are host cells harboring a universal GPCR reporter construct of the invention, as well as assays for detecting modulators of GPCRs using the host cells.