Patent ID: 7235374

Claim:
A method of assessing the effect of a test condition on G-protein-coupled receptor (GPCR) pathway activity, comprising: a) providing a cell that expresses a GPCR as a fusion protein to one mutant form of reporter enzyme and an interacting protein partner as a fusion to another mutant form of enzyme; wherein said GPCR fusion protein is modified to include one or more sets of serine/threonine clusters, wherein said one or more sets of serine/threonine clusters enhance binding of said GPCR to arrestin, wherein said enhanced binding between said GPCR and said arrestin increases sensitivity of detection of said effect of said test condition; b) exposing the cell to a ligand for said GPCR under said test condition; and c) monitoring activation of said GPCR by complementation of said reporter enzyme; wherein increased reporter enzyme activity in the cell compared to that which occurs in the absence of said test condition indicates increased GPCR interaction with interacting protein partner compared to that which occurs in the absence of said test condition, and decreased reporter enzyme activity in the cell compared to that which occurs in the absence of said test condition indicates decreased GPCR interaction with interacting protein partner compared to that which occurs in the absence of said test condition.