GPR54 undergoes GRK2-dependent desensitization (A) FLAG-GPR54-stimulated IP formation in response to increasing concentrations of Kp-10 at 37 C in either the absence (closed circles) or the presence (open circles) of wild-type GRK2 or K220R (open triangles). The data points represent the mean ± se for three to six independent experiments. B, Representative autoradiograph demonstrating the whole-cell phosphorylation of FLAG-GPR54 treated with 100 nm Kp-10 for 10 min in the presence and absence of GRK2 or K220R. C, Basal IP formation in nontransfected (NT) vs. FLAG-GPR54-expressing HEK 293 cells. Data are expressed as a percentage of the maximal Kp-10-stimulated response observed in HEK 293 cells expressing FLAG-GPR54. The data represent the mean ± se for nine independent experiments. ***, P < 0.0001 vs. NT (D) The effect of GRK2 and K220R on basal GPR54 activity in HEK 293 cells. The data represent the mean ± se for three to six independent experiments. ***, P < 0.001 vs. control; ΔΔΔ, P < 0.001 vs. GRK2. E, Relative cell surface expression of FLAG-GPR54 in HEK 293 cells in the presence or absence of GRK2. Cell surface expression was determined by flow cytometry and represents the mean cell surface fluorescence. The data represents the mean ± se for three independent experiments. F, Time course for GPR54 basal or constitutive (closed symbols) and Kp-10-stimulated (open symbols) internalization in the absence (circles) or presence (triangles) of GRK2. The data represent the mean ± se of three to nine independent experiments. In all of the experiments, HEK 293 cells were transiently transfected with 10 μg of receptor and with 5 μg of either empty plasmid vector or plasmid cDNA encoding GRK2 or K220R.