Document Detail


Modulation of subfamily B/R4 RGS protein function by 14-3-3 proteins.
MedLine Citation:
PMID:  16839744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Maria Abramow-Newerly; Hong Ming; Peter Chidiac
Related Documents :
14502984 - Understanding the functions of plant disease resistance proteins.
12930894 - Short- and long-range effects of sonic hedgehog in limb development.
16246064 - Compartmentation of g-protein-coupled receptors and their signalling components in lipi...
20876874 - Coupling mechanism of a gpcr and a heterotrimeric g protein during chemoattractant grad...
19751674 - The effect of different force applications on the protein-protein complex barnase-barstar.
75194 - The effect of biogenic monomines on rapid axonal transport in the rabbit optic nerve.
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    
Affiliation:
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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
Humans
Hydrolysis
Immunoblotting
Kinetics
Leucine / metabolism
Microscopy, Confocal
Protein Binding / physiology
Protein Isoforms / genetics,  metabolism
RGS Proteins / genetics,  metabolism*,  physiology
Recombinant Fusion Proteins / genetics,  metabolism
Transfection
Tyrosine / metabolism
Chemical
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 2.5.1.18/Glutathione Transferase; EC 3.6.1.-/GTP-Binding Proteins

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


Previous Document:  Novel mechanisms of the regulation of protein kinase B in adipocytes; implications for protein kinas...
Next Document:  Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation ...