Modulation of subfamily B/R4 RGS protein function by 14-3-3 proteins

被引:28
作者
Abramow-Newerly, Maria [1 ]
Ming, Hong [1 ]
Chidiac, Peter [1 ]
机构
[1] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada
基金
加拿大健康研究院;
关键词
14-3-3; G protein; G protein-coupled receptor signalling; regulator of G protein signalling (RGS) protein; GTPase activating protein (GAP); molecular chelator;
D O I
10.1016/j.cellsig.2006.05.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Regulator of G protein signalling (RGS) proteins are primarily known for their ability to act as GTPase activating proteins (GAPs) and thus attenuate G protein function within G protein-coupled receptor (GPCR) signalling pathways. However, RGS proteins have been found to interact with additional binding partners, and this has introduced more complexity to our understanding of their potential role in vivo. Here, we identify a novel interaction between RGS proteins (RGS4, RGS5, RGS16) and the multifunctional protein 14-3-3. Two isoforms, 14-3-3 beta and 14-3-3 epsilon, directly interact with all three purified RGS proteins and data from in vitro steady state GTP hydrolysis assays show that 14-3-3 inhibits the GTPase activity of RGS4 and RGS16, but has limited effects on RGS5 under comparable conditions. Moreover in a competitive pull-down experiment, 14-3-3 epsilon competes with G epsilon o for RGS4, but not for RGS5. This mechanism is further reinforced in living cells, where 14-3-3 epsilon sequesters RGS4 in the cytoplasm and impedes its recruitment to the plasma membrane by G alpha protein. Thus, 14-3-3 might act as a molecular chelator, preventing RGS proteins from interacting with G alpha, and ultimately prolonging the signal transduction pathway. In conclusion, our findings suggest that 14-3-3 proteins may indirectly promote GPCR signalling via their inhibitory effects on RGS GAP function. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:2209 / 2222
页数:14
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