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 analysis of RGS expression, we reveal biphasic effects of RGSs on GIRK regulation. At low concentrations, RGS4 inhibited basal GIRK activity, but stimulated it at high concentrations. RGS7, which is associated with the G protein subunit G beta 5, is regulated by G beta 5 by two distinct mechanisms. First, G beta 5 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 supplementary to their GTPase-activating protein activity.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel. raifmant@yahoo.com
T
T
Keren-Raifman
A K
AK
Bera
D
D
Zveig
S
S
Peleg
D S
DS
Witherow
V Z
VZ
Slepak
N
N
Dascal
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D009865:Oocytes; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D020710:RGS Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits; D020690:GTPase-Activating Proteins; C490610:Gnb5 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020710:RGS Proteins; C492038:Rgs7 protein, mouse; C098799:RGS4 protein; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins