G-protein-coupled receptor kinase 2 (GRK2) is a serine/ threonine kinase with an important function in the desensitization of G-protein-coupled receptors. Based on its ability to bind G-protein bg subunits as well as activated Ga q subunits, it can be considered as an effector for G-proteins. The recruitment of GRK2 to activated receptors is well known to be mediated by Gbg together with negatively charged membrane phospholipids. In the current study, we address the role of Ga q on the interaction of GRK2 with activated G q -protein-coupled receptors. Therefore, we established new Förster resonance energy transfer (FRET)-based assays to study the interaction of GRK2 with the M 3 -acetylcholine (M 3 -ACh) receptor as well as G q -protein subunits with high spatiotemporal resolution in single living human embryonic kidney 293T cells. M 3 -ACh receptor stimulation with 10 mM acetylcholine resulted in distinct changes in FRET, which reflects interaction of the respective proteins. GRK2 mutants with reduced binding affinity toward Ga q [GRK2(D110A)] and Gbg [GRK2(R587Q)] were used to determine the specific role of G q -protein-binding by GRK2. Comparison of absolute FRET amplitudes demonstrated that Ga q enhances the extent and stability of the GRK2-M 3 -ACh receptor interaction, and that not only Gbg but also Ga q can target GRK2 to the membrane. This reveals an important role of Ga q in efficient recruitment of GRK2 to M 3 -ACh receptors. Furthermore, interactions between Ga q and GRK2 were associated with a prolongation of the interaction between GRK2 and the M 3 -ACh receptor and enhanced arrestin recruitment by these receptors, indicating that Ga q influences signaling and desensitization.