Sensitive assays for candidate compounds affecting GPCR activity are provided using a cell containing fusion proteins comprising a first fusion protein comprising (a) a target GPCR fused to a small fragment of ß-galactosidase through a linker comprising a phosphorylation site or (b) a GPCR or a protein of interest, where the GPCR and protein of interest form a complex and one of them is fused to the small fragment of ß-galactosidase; and a second fusion protein comprising arrestin fused to a large fragment of ß-galactosidase. In (a), the affinity of the small and large fragments is optimized based on the background to signal ratio and the absolute signal observed. The assay is performed using a ß-galactosidase substrate that provides a detectable optical signal.
GPCR ARRESTIN ASSAYS