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 Gβ5

FEBS Letters

Dascal, Nathan²  Keren-Raifman, Tal²  Peleg, Sagit²  Witherow, D.Scott¹  Bera, Amal K.²  Zveig, Dror²  Slepak, Vladlen Z.¹ 

[1] Department of Molecular and Cellular Pharmacology and the Neuroscience Program, University of Miami School of Medicine, Miami, FL, USA;Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel

关键词: G protein;    Regulator of G protein signaling;    G protein-activated K+ channel;    Potassium channel;    Gβ5;    Xenopus oocyte;    ACh;    acetylcholine;    GAP;    GTPase-activating protein;    GGL;    G protein γ-like (domain);    GIRK;    G protein-activated K+ channels;    I ACh;    agonist-evoked GIRK current;    I hK;    basal GIRK current;    RGS;    regulator of G protein signaling;   

DOI  :  10.1016/S0014-5793(01)02220-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Gβ5, is regulated by Gβ5 by two distinct mechanisms. First, Gβ5 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.

【 授权许可】

Unknown