Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Biol. Chem. 277 (51): 49888-49895

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

The beta gamma Subunit of Heterotrimeric G Proteins Interacts with RACK1 and Two Other WD Repeat Proteins*

Edward J. DellDagger , Jennifer ConnorDagger , Songhai Chen§, Elizabeth G. Stebbins, Nikolai P. SkibaDagger , Daria Mochly-Rosen, and Heidi E. HammDagger §||

From the Dagger  Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60613, the  Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5174, and the § Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600

A yeast two-hybrid approach was used to discern possible new effectors for the beta gamma subunit of heterotrimeric G proteins. Three of the clones isolated are structurally similar to Gbeta , each exhibiting the WD40 repeat motif. Two of these proteins, the receptor for activated C kinase 1 (RACK1) and the dynein intermediate chain, co-immunoprecipitate with Gbeta gamma using an anti-Gbeta antibody. The third protein, AAH20044, has no known function; however, sequence analysis indicates that it is a WD40 repeat protein. Further investigation with RACK1 shows that it not only interacts with Gbeta 1gamma 1 but also unexpectedly with the transducin heterotrimer Galpha tbeta 1gamma 1. Galpha t alone does not interact, but it must contribute to the interaction because the apparent EC50 value of RACK1 for Galpha tbeta 1gamma 1 is 3-fold greater than that for Gbeta 1gamma 1 (0.1 versus 0.3 µM). RACK1 is a scaffold that interacts with several proteins, among which are activated beta IIPKC and dynamin-1 (1). beta IIPKC and dynamin-1 compete with Gbeta 1gamma 1 and Galpha tbeta 1gamma 1 for interaction with RACK1. These findings have several implications: 1) that WD40 repeat proteins may interact with each other; 2) that Gbeta gamma interacts differently with RACK1 than with its other known effectors; and/or 3) that the G protein-RACK1 complex may constitute a signaling scaffold important for intracellular responses.

* This work was supported by Grant EY100291 from the National Institutes of Health (to H. E. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed. Tel.: 615-343-3533; Fax: 615-343-1084; E-mail: heidi.hamm@vanderbilt.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pleiotropic Roles of the Msi1-Like Protein Msl1 in Cryptococcus neoformans.
D.-H. Yang, S. Maeng, A. K. Strain, A. Floyd, K. Nielsen, J. Heitman, and Y.-S. Bahn (2012)
Eukaryot. Cell 11, 1482-1495
   Abstract »    Full Text »    PDF »
Protein Kinase C (PKC) Activity Regulates Functional Effects of Kv{beta}1.3 Subunit on KV1.5 Channels: IDENTIFICATION OF A CARDIAC Kv1.5 CHANNELOSOME.
M. David, A. Macias, C. Moreno, A. Prieto, R. Martinez-Marmol, R. Vicente, T. Gonzalez, A. Felipe, M. M. Tamkun, and C. Valenzuela (2012)
J. Biol. Chem. 287, 21416-21428
   Abstract »    Full Text »    PDF »
The WD40 Repeat Protein WDR26 Binds G{beta}{gamma} and Promotes G{beta}{gamma}-dependent Signal Transduction and Leukocyte Migration.
Z. Sun, X. Tang, F. Lin, and S. Chen (2011)
J. Biol. Chem. 286, 43902-43912
   Abstract »    Full Text »    PDF »
Understanding Molecular Recognition by G protein {beta}{gamma} Subunits on the Path to Pharmacological Targeting.
Y. Lin and A. V. Smrcka (2011)
Mol. Pharmacol. 80, 551-557
   Abstract »    Full Text »    PDF »
Involvement of Arabidopsis RACK1 in Protein Translation and Its Regulation by Abscisic Acid.
J. Guo, S. Wang, O. Valerius, H. Hall, Q. Zeng, J.-F. Li, D. J. Weston, B. E. Ellis, and J.-G. Chen (2011)
Plant Physiology 155, 370-383
   Abstract »    Full Text »    PDF »
Epigenetic Regulation of BDNF Expression via the Scaffolding Protein RACK1.
D.-Y. He, J. Neasta, and D. Ron (2010)
J. Biol. Chem. 285, 19043-19050
   Abstract »    Full Text »    PDF »
N Terminus of Type 5 Adenylyl Cyclase Scaffolds Gs Heterotrimer.
R. Sadana, N. Dascal, and C. W. Dessauer (2009)
Mol. Pharmacol. 76, 1256-1264
   Abstract »    Full Text »    PDF »
The G protein {beta}{gamma} subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin.
N. Knezevic, M. Tauseef, T. Thennes, and D. Mehta (2009)
J. Exp. Med. 206, 2761-2777
   Abstract »    Full Text »    PDF »
Dissection of the Relationship Between RACK1 and Heterotrimeric G-Proteins in Arabidopsis.
J. Guo, S. Wang, J. Wang, W.-D. Huang, J. Liang, and J.-G. Chen (2009)
Plant Cell Physiol. 50, 1681-1694
   Abstract »    Full Text »    PDF »
Differential Gene Expression in the Bovine Corpus Luteum During Transition from Early Phase to Midphase and Its Potential Role in Acquisition of Luteolytic Sensitivity to Prostaglandin F2 Alpha.
M. P. Goravanahally, M. Salem, J. Yao, E. K. Inskeep, and J. A. Flores (2009)
Biol Reprod 80, 980-988
   Abstract »    Full Text »    PDF »
Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels.
S. Dai, D. D. Hall, and J. W. Hell (2009)
Physiol Rev 89, 411-452
   Abstract »    Full Text »    PDF »
RACK-1 Directs Dynactin-dependent RAB-11 Endosomal Recycling during Mitosis in Caenorhabditis elegans.
E. Ai, D. S. Poole, and A. R. Skop (2009)
Mol. Biol. Cell 20, 1629-1638
   Abstract »    Full Text »    PDF »
The RACK1 Ortholog Asc1 Functions as a G-protein beta Subunit Coupled to Glucose Responsiveness in Yeast.
C. E. Zeller, S. C. Parnell, and H. G. Dohlman (2007)
J. Biol. Chem. 282, 25168-25176
   Abstract »    Full Text »    PDF »
Gib2, A Novel Gbeta-like/RACK1 Homolog, Functions as a Gbeta Subunit in cAMP Signaling and Is Essential in Cryptococcus neoformans.
D. A. Palmer, J. K. Thompson, L. Li, A. Prat, and P. Wang (2006)
J. Biol. Chem. 281, 32596-32605
   Abstract »    Full Text »    PDF »
RACK1 mediates multiple hormone responsiveness and developmental processes in Arabidopsis.
J.-G. Chen, H. Ullah, B. Temple, J. Liang, J. Guo, J. M. Alonso, J. R. Ecker, and A. M. Jones (2006)
J. Exp. Bot. 57, 2697-2708
   Abstract »    Full Text »    PDF »
Genome-Scale Analysis Reveals Sst2 as the Principal Regulator of Mating Pheromone Signaling in the Yeast Saccharomyces cerevisiae.
S. A. Chasse, P. Flanary, S. C. Parnell, N. Hao, J. Y. Cha, D. P. Siderovski, and H. G. Dohlman (2006)
Eukaryot. Cell 5, 330-346
   Abstract »    Full Text »    PDF »
Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gbeta{gamma}.
M. Sato, M. J. Cismowski, E. Toyota, A. V. Smrcka, P. A. Lucchesi, W. M. Chilian, and S. M. Lanier (2006)
PNAS 103, 797-802
   Abstract »    Full Text »    PDF »
G{beta}{gamma} Binds Histone Deacetylase 5 (HDAC5) and Inhibits Its Transcriptional Co-repression Activity.
B. D. Spiegelberg and H. E. Hamm (2005)
J. Biol. Chem. 280, 41769-41776
   Abstract »    Full Text »    PDF »
RACK1 Binds to a Signal Transfer Region of G{beta}{gamma} and Inhibits Phospholipase C {beta}2 Activation.
S. Chen, F. Lin, and H. E. Hamm (2005)
J. Biol. Chem. 280, 33445-33452
   Abstract »    Full Text »    PDF »
Proteomic Characterization of Evolutionarily Conserved and Variable Proteins of Arabidopsis Cytosolic Ribosomes.
I.-F. Chang, K. Szick-Miranda, S. Pan, and J. Bailey-Serres (2005)
Plant Physiology 137, 848-862
   Abstract »    Full Text »    PDF »
Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy.
R. Arya, V. Kedar, J. R. Hwang, H. McDonough, H.-H. Li, J. Taylor, and C. Patterson (2004)
J. Cell Biol. 167, 1147-1159
   Abstract »    Full Text »    PDF »
Yeast Asc1p and Mammalian RACK1 Are Functionally Orthologous Core 40S Ribosomal Proteins That Repress Gene Expression.
V. R. Gerbasi, C. M. Weaver, S. Hill, D. B. Friedman, and A. J. Link (2004)
Mol. Cell. Biol. 24, 8276-8287
   Abstract »    Full Text »    PDF »
Spatial and Temporal Regulation of RACK1 Function and N-methyl-D-aspartate Receptor Activity through WD40 Motif-mediated Dimerization.
C. Thornton, K.-C. Tang, K. Phamluong, K. Luong, A. Vagts, D. Nikanjam, R. Yaka, and D. Ron (2004)
J. Biol. Chem. 279, 31357-31364
   Abstract »    Full Text »    PDF »
Coordination of Membrane Excitability through a GIRK1 Signaling Complex in the Atria.
E. N. Nikolov and T. T. Ivanova-Nikolova (2004)
J. Biol. Chem. 279, 23630-23636
   Abstract »    Full Text »    PDF »
RACK1 Regulates Specific Functions of G{beta}{gamma}.
S. Chen, E. J. Dell, F. Lin, J. Sai, and H. E. Hamm (2004)
J. Biol. Chem. 279, 17861-17868
   Abstract »    Full Text »    PDF »
RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release.
R. L. Patterson, D. B. van Rossum, R. K. Barrow, and S. H. Snyder (2004)
PNAS 101, 2328-2332
   Abstract »    Full Text »    PDF »
Insights into G Protein Structure, Function, and Regulation.
T. M. Cabrera-Vera, J. Vanhauwe, T. O. Thomas, M. Medkova, A. Preininger, M. R. Mazzoni, and H. E. Hamm (2003)
Endocr. Rev. 24, 765-781
   Abstract »    Full Text »    PDF »
Leishmania major LACK Antigen Is Required for Efficient Vertebrate Parasitization.
B. L. Kelly, D. B. Stetson, and R. M. Locksley (2003)
J. Exp. Med. 198, 1689-1698
   Abstract »    Full Text »    PDF »
Alternative Splicing of the Human Proto-oncogene c-H-ras Renders a New Ras Family Protein That Trafficks to Cytoplasm and Nucleus.
S. Guil, N. de La Iglesia, J. Fernandez-Larrea, D. Cifuentes, J. C. Ferrer, J. J. Guinovart, and M. Bach-Elias (2003)
Cancer Res. 63, 5178-5187
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882