PHOSPHOLIPASE C-BETA-1 IS A GTPASE-ACTIVATING PROTEIN FOR GQ/11, ITS PHYSIOLOGICAL REGULATOR

被引:356
作者
BERSTEIN, G
BLANK, JL
JHON, DY
EXTON, JH
RHEE, SG
ROSS, EM
机构
[1] VANDERBILT UNIV, MED CTR,SCH MED,HOWARD HUGHES MED INST, DEPT MOLEC PHYSIOL & BIOPHYS, NASHVILLE, TN 37232 USA
[2] NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA
关键词
D O I
10.1016/0092-8674(92)90165-9
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
Purified M1 muscarinic cholinergic receptor and G(q/11) were coreconstituted in lipid vesicles. Addition of purified phospholipase C-beta-1 (PLC-beta-1) further stimulated the receptor-promoted steady-state GTPase activity of G(q/11) up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-beta-1 caused a rapid burst of hydrolysis of G(q/11)-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta-1 stimulates hydrolysis of G(q/11)-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, G(q/11). GTPase-stimulating activity was specific both for PLC-beta-1 and G(g/11). Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.
引用
收藏
页码:411 / 418
页数:8
相关论文
共 45 条
[1]   GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN (GAP) INTERACTS WITH THE P21-RAS EFFECTOR BINDING DOMAIN [J].
ADARI, H ;
LOWY, DR ;
WILLUMSEN, BM ;
DER, CJ ;
MCCORMICK, F .
SCIENCE, 1988, 240 (4851) :518-520
[2]  
ARSHAVSKY VY, 1991, J BIOL CHEM, V266, P18530
[3]  
BERSTEIN G, 1992, J BIOL CHEM, V267, P8081
[4]  
BLANK JL, 1991, J BIOL CHEM, V266, P18206
[5]  
BOLLAG G, 1991, ANNU REV CELL BIOL, V7, P601, DOI 10.1146/annurev.cellbio.7.1.601
[6]  
BOURNE HR, 1991, NATURE, V349, P117, DOI 10.1038/349117a0
[7]   THE GTPASE SUPERFAMILY - A CONSERVED SWITCH FOR DIVERSE CELL FUNCTIONS [J].
BOURNE, HR ;
SANDERS, DA ;
MCCORMICK, F .
NATURE, 1990, 348 (6297) :125-132
[8]  
BRANDT DR, 1985, J BIOL CHEM, V260, P266
[9]  
BRANDT DR, 1986, J BIOL CHEM, V261, P1656
[10]   MECHANISM OF MUSCARINIC RECEPTOR INDUCED K+ CHANNEL ACTIVATION AS REVEALED BY HYDROLYSIS-RESISTANT GTP ANALOGS [J].
BREITWIESER, GE ;
SZABO, G .
JOURNAL OF GENERAL PHYSIOLOGY, 1988, 91 (04) :469-493