Phosphorylation and nuclear translocation of a regulator of G protein signaling (RGS10)

Heterotrimeric G proteins are involved in the transduction of hormonal and sensory signals across plasma membranes of eukaryotic cells. Hence, they ar e a critical point of control for a variety of agents that modulate cellula r function. Activation of these proteins is dependent on GTP binding to the ir alpha (G alpha) subunits. Regulators of G protein signaling (RGS) bind s pecifically to activated G alpha proteins, potentiating the intrinsic GTPas e activity of the Ga proteins and thus expediting the termination of Ga sig naling. Although there are several points in most G protein controlled sign aling pathways that are affected by reversible covalent modification, littl e evidence has been shown addressing whether or not the functions of RGS pr oteins are themselves regulated by such modifications. We report in this st udy the acute functional regulation of RGS10 thru the specific and inducibl e phosphorylation of RGS10 protein at serine 168 by cAMP-dependent kinase A . This phosphorylation nullifies the RGS10 activity at the plasma membrane, which controls the G protein-dependent activation of the inwardly rectifyi ng potassium channel. Surprisingly, the phosphorylation-mediated attenuatio n of RGS10 activity was not manifested in an alteration of its ability to a ccelerate GTPase activity of Ga. Rather, the phosphorylation event correlat es with translocation of RGS10 from the plasma membrane and cytosol into th e nucleus.