RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity

被引:125
作者
Hooks, SB
Waldo, GL
Corbitt, J
Bodor, ET
Krumins, AM
Harden, TK
机构
[1] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA
[2] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA
关键词
D O I
10.1074/jbc.M211382200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulator of G-protein signaling (RGS) proteins are GTPase activating proteins (GAPs) of heterotrimeric G-proteins that alter the amplitude and kinetics of receptor-promoted signaling. In this study we defined the G-protein alpha-subunit selectivity of purified Sf9 cell-derived R7 proteins, a subfamily of RGS proteins (RGS6,-7, -9, and -11) containing a Ggamma-like (GGL) domain that mediates dimeric interaction with Gbeta(5). Gbeta(5)/R7 dimers stimulated steady state GTPase activity of Galpha-subunits of the G(i) family, but not of Galpha(q) or Galpha(11), when added to proteoliposomes containing M2 or M1 muscarinic receptor-coupled G-protein heterotrimers. Concentration effect curves of the Gbeta(5)/R7 proteins revealed differences in potencies and efficacies toward Galpha-subunits of the G(i) family. Although all four Gbeta(5)/R7 proteins exhibited similar potencies toward Galpha(o), Gbeta(5)/RGS9 and Gbeta(5)/RGS11 were more potent GAPs of Galpha(i1), Galpha(i2), and Galpha(i3), than were Gbeta(5)/RGS6 and Gbeta(5)/RGS7. The maximal GAP activity exhibited by Gbeta(5)/RGS11 was 2- to 4-fold higher than that of Gbeta(5)/RGS7 and Gbeta(5)/RGS9, with Gbeta(5)/RGS6 exhibiting an intermediate maximal GAP activity. Moreover, the less efficacious Gbeta(5)/RGS7 and Gbeta(5)/RGS9 inhibited Gbeta(5)/RGS11-stimulated GTPase activity of Galpha(o). Therefore, R7 family RGS proteins are G(i) family-selective GAPs with potentially important differences in activities.
引用
收藏
页码:10087 / 10093
页数:7
相关论文
共 50 条
[41]   Fidelity of G protein β-subunit association by the G protein γ-subunit-like domains of RGS6, RGS7, and RGS11 [J].
Snow, BE ;
Betts, L ;
Mangion, J ;
Sondek, J ;
Siderovski, DP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :6489-6494
[42]   Gγ-like (CG-L) domains:: new frontiers in G-protein signaling and β-propeller scaffolding [J].
Sondek, J ;
Siderovski, DP .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (11) :1329-1337
[43]   Structure of RGS4 bound to AlF4--activated G(i alpha 1): Stabilization of the transition state for GTP hydrolysis [J].
Tesmer, JJG ;
Berman, DM ;
Gilman, AG ;
Sprang, SR .
CELL, 1997, 89 (02) :251-261
[44]  
Watts VJ, 1998, J NEUROSCI, V18, P8692
[45]  
Weiner DM, 2001, J PHARMACOL EXP THER, V299, P268
[46]   Complexes of the G protein subunit Gβ5 with the regulators of G protein signaling RGS7 and RGS9 -: Characterization in native tissues and in transfected cells [J].
Witherow, DS ;
Wang, Q ;
Levay, K ;
Cabrera, JL ;
Chen, J ;
Willars, GB ;
Slepak, VZ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (32) :24872-24880
[47]   RGS proteins determine signaling specificity of Gq-coupled receptors [J].
Xu, X ;
Zeng, WH ;
Popov, S ;
Berman, DM ;
Davignon, I ;
Yu, K ;
Yowe, D ;
Offermanns, S ;
Muallem, S ;
Wilkie, TM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (06) :3549-3556
[48]   The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling [J].
Zeng, WZ ;
Xu, X ;
Popov, S ;
Mukhopadhyay, S ;
Chidiac, P ;
Swistok, J ;
Danho, W ;
Yagaloff, KA ;
Fisher, SL ;
Ross, EM ;
Muallem, S ;
Wilkie, TM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (52) :34687-34690
[49]   RGS-PX1, a GAP for Gαs and sorting nexin in vesicular trafficking [J].
Zheng, B ;
Ma, YC ;
Ostrom, RS ;
Lavoie, C ;
Gill, GN ;
Insel, PA ;
Huang, XY ;
Farquhar, MG .
SCIENCE, 2001, 294 (5548) :1939-1942
[50]  
Zhong HL, 2001, J PHARMACOL EXP THER, V297, P837