Publications
대표논문
Date: December 23, 1998

Journal: Journal of Biological Chemistry Volume 274, Issue 13, 26 March 1999, Pages 8770-8778 , Doi: 10.1074/jbc.274.13.8770

1998 | The α-helical domain of Gα(t) determines specific interaction with regulator of G protein signaling 9…

Nikolai P. Skiba, Chii-Shen Yang, Tao Huang, Hyunsu Bae and Heidi E. Hamm

Abstract

RGS proteins (regulators of G protein signaling) are potent accelerators of the intrinsic GTPase activity of G protein α subunits (GAPs), thus controlling the response kinetics of a variety of cell signaling processes. Most RGS domains that have been studied have relatively little GTPase activating specificity especially for G proteins within the Gi subfamily. Retinal RGS9 is unique in its ability to act synergistically with a downstream effector cGMP phosphodiesterase to stimulate the GTPase activity of the α subunit of transducin, Gαt. Here we report another unique property of RGS9: high specificity for Gαt. The core (RGS) domain of RGS9 (RGS9) stimulates Gαt GTPase activity by 10-fold and Gαi1 GTPase activity by only 2-fold at a concentration of 10 μm. Using chimeric Gαt/Gαi1 subunits we demonstrated that the α-helical domain of Gαt imparts this specificity. The functional effects of RGS9 were well correlated with its affinity for activated Gα subunits as measured by a change in fluorescence of a mutant Gαt (Chi6b) selectively labeled at Cys-210.K d values for RGS9 complexes with Gαtand Gαi1 calculated from the direct binding and competition experiments were 185 nm and 2 μm, respectively. The γ subunit of phosphodiesterase increases the GAP activity of RGS9. We demonstrate that this is because of the ability of Pγ to increase the affinity of RGS9 for Gαt. A distinct, nonoverlapping pattern of RGS and Pγ interaction with Gαt suggests a unique mechanism of effector-mediated GAP function of the RGS9.  


TITLE
 The α-helical domain of Gα(t) determines specific interaction with regulator of G protein signaling 9
JOURNAL
 Journal of Biological Chemistry
 Volume 274, Issue 13, 26 March 1999, Pages 8770-8778
 DOI
 10.1074/jbc.274.13.8770 (click 하시면 DOI 검색 결과가 새창으로 나타납니다.)
 
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