Document Detail

Modulation of subfamily B/R4 RGS protein function by 14-3-3 proteins.
MedLine Citation:
PMID:  16839744     Owner:  NLM     Status:  MEDLINE    
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, 14-3-3beta and 14-3-3epsilon, 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, 14-3-3epsilon competes with Galphao for RGS4, but not for RGS5. This mechanism is further reinforced in living cells, where 14-3-3epsilon sequesters RGS4 in the cytoplasm and impedes its recruitment to the plasma membrane by Galpha protein. Thus, 14-3-3 might act as a molecular chelator, preventing RGS proteins from interacting with Galpha, 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.
Maria Abramow-Newerly; Hong Ming; Peter Chidiac
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-23
Journal Detail:
Title:  Cellular signalling     Volume:  18     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-10-31     Completed Date:  2007-02-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  2209-22     Citation Subset:  IM    
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
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MeSH Terms
14-3-3 Proteins / genetics,  metabolism*
Binding Sites
Binding, Competitive
Cell Extracts / chemistry
Cell Line
GTP-Binding Proteins / genetics,  metabolism
GTPase-Activating Proteins / metabolism
Glutathione Transferase / genetics,  metabolism
Green Fluorescent Proteins / genetics,  metabolism
Guanosine Triphosphate / metabolism
Leucine / metabolism
Microscopy, Confocal
Protein Binding / physiology
Protein Isoforms / genetics,  metabolism
RGS Proteins / genetics,  metabolism*,  physiology
Recombinant Fusion Proteins / genetics,  metabolism
Tyrosine / metabolism
Reg. No./Substance:
0/14-3-3 Proteins; 0/Cell Extracts; 0/GTPase-Activating Proteins; 0/Protein Isoforms; 0/RGS Proteins; 0/Recombinant Fusion Proteins; 147336-22-9/Green Fluorescent Proteins; 55520-40-6/Tyrosine; 61-90-5/Leucine; 86-01-1/Guanosine Triphosphate; EC Transferase; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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