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 expressed in human embryonic kidney 293 cells localized to the nucleus and cytosol, respectively. They were selectively recruited to the plasma membrane by G proteins and correspondingly by receptors that activate those G proteins: GFP-RGS2 when coexpressed with Galphas, beta2-adrenergic receptor, Galphaq, or AT1A angiotensin II receptor, and GFP-RGS4 when coexpressed with Galphai2 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 proteins and is independent of downstream signaling events.