Recruitment of RGS2 and RGS4 to the plasma membrane by G proteins and receptors reflects functional interactions

N-terminally green fluorescent protein (GFP)-tagged regulator of G protein signaling (RGS) 2 and RGS4 fusion proteins ex-pressed in human embryonic kidney 293 cells localized to the nucleus and cytosol, respectively. They were selectively re-cruited to the plasma membrane by G proteins and corre-spondingly by receptors that activate those G proteins: GFP-RGS2 when coexpressed with Gs, 2-adrenergic receptor, Gq, or AT1A angiotensin II receptor, and GFP-RGS4 when coexpressed with Gi2 or M2 muscarinic receptor. G protein mutants with reduced RGS affinity did not produce this effect, implying that the recruitment involves direct binding to G pro-teins and is independent of downstream signaling events. Nei-ther agonists nor inverse agonists altered receptor-promoted RGS association with the plasma membrane, and expressin