The invention provides a method for selectively activating a target cell, where the target cell expresses a receptor activated superiorly by a synthetic ligand (RASSL) having decreased binding affinity for a selected natural ligand and normal or near normal binding affinity for a synthetic small molecule agonist. Thus, RASSL-mediated activation of target cells does not occur to a significant extent in the presence of natural G protein-coupled receptor ligand, but is significantly stimulated upon exposure to a synthetic small molecule. RASSL-expressing target cells are selectively activated by exposing of the cells to an appropriate synthetic small molecule, which in turn binds the RASSL, resulting in G protein activation and triggering of a specific cellular response associated with G protein activation (e.g., cellular proliferation or cellular secretion).