Expression levels of RGS7 and RGS4 proteins determine the mode of regulation of the G protein-activated K+ channel and control regulation of RGS7 by G beta 5

Regulators of G protein signaling RGS4 and RGS7 accelerate the kinetics of K+ channels (GIRKs) in the Xenopus oocyte system. Here, via quantitative an alysis of RGS expression, we reveal biphasic effects of RGSs on GIRK regula tion, At low concentrations, RGS4 inhibited basal GIRK activity, but stimul ated it at high concentrations. RGS7, which is associated with the G protei n subunit G beta5, is regulated by G beta5 by two distinct mechanisms. Firs t, G beta5 augments RGS7 activity. and second, it increases its expression. These dual effects resolve previous controversies regarding RGS4 and RGS7 function and indicate that they modulate signaling by mechanisms supplement ary to their GTPase-activating protein activity, (C) 2001 Federation of Eur opean Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.