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Endocrine Reviews 24 (6): 765-781
Copyright © 2003 by The Endocrine Society

Insights into G Protein Structure, Function, and Regulation

Theresa M. Cabrera-Vera, Jurgen Vanhauwe, Tarita O. Thomas, Martina Medkova, Anita Preininger, Maria R. Mazzoni and Heidi E. Hamm

Department of Molecular Pharmacology and Biological Chemistry (T.M.C.-V., J.V., T.O.T., M.M., A.P., H.E.M.), Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611; Department of Molecular Pharmacology (M.R.M., H.E.M.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; and Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology (M.R.M.), University of Pisa, Pisa, 56057, Italy

Correspondence: Address all correspondence and requests for reprints to: Heidi E. Hamm, Ph.D., Department of Pharmacology, Vanderbilt University Medical Center, 442 Robinson Research Building, 23rd and Pierce Drive, Nashville, Tennessee 37232. E-mail: heidi.hamm{at}mcmail.vanderbilt.edu

In multicellular organisms from Caenorhabditis elegans to Homo sapiens, the maintenance of homeostasis is dependent on the continual flow and processing of information through a complex network of cells. Moreover, in order for the organism to respond to an ever-changing environment, intercellular signals must be transduced, amplified, and ultimately converted to the appropriate physiological response. The resolution of the molecular events underlying signal response and integration forms the basis of the signal transduction field of research. An evolutionarily highly conserved group of molecules known as heterotrimeric guanine nucleotide-binding proteins (G proteins) are key determinants of the specificity and temporal characteristics of many signaling processes and are the topic of this review. Numerous hormones, neurotransmitters, chemokines, local mediators, and sensory stimuli exert their effects on cells by binding to heptahelical membrane receptors coupled to heterotrimeric G proteins. These highly specialized transducers can modulate the activity of multiple signaling pathways leading to diverse biological responses. In vivo, specific combinations of G{alpha}- and Gß{gamma}-subunits are likely required for connecting individual receptors to signaling pathways. The structural determinants of receptor-G protein-effector specificity are not completely understood and, in addition to involving interaction domains of these primary acting proteins, also require the participation of scaffolding and regulatory proteins.




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S. A. Andric, D. Zivadinovic, A. E. Gonzalez-Iglesias, A. Lachowicz, M. Tomic, and S. S. Stojilkovic
Endothelin-induced, Long Lasting, and Ca2+ Influx-independent Blockade of Intrinsic Secretion in Pituitary Cells by Gz Subunits
J. Biol. Chem., July 22, 2005; 280(29): 26896 - 26903.
[Abstract] [Full Text] [PDF]


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JCBHome page
T. Kino, A. Tiulpakov, T. Ichijo, L. Chheng, T. Kozasa, and G. P. Chrousos
G protein {beta} interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus
J. Cell Biol., June 20, 2005; 169(6): 885 - 896.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
L. Wang, C. G. Radu, L. V. Yang, L. A. Bentolila, M. Riedinger, and O. N. Witte
Lysophosphatidylcholine-induced Surface Redistribution Regulates Signaling of the Murine G Protein-coupled Receptor G2A
Mol. Biol. Cell, May 1, 2005; 16(5): 2234 - 2247.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
E. Kostenis, L. Martini, J. Ellis, M. Waldhoer, A. Heydorn, M. M. Rosenkilde, P. K. Norregaard, R. Jorgensen, J. L. Whistler, and G. Milligan
A Highly Conserved Glycine within Linker I and the Extreme C Terminus of G Protein {alpha} Subunits Interact Cooperatively in Switching G Protein-Coupled Receptor-to-Effector Specificity
J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 78 - 87.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
W.-C. Chung and J. C. Kermode
Suramin Disrupts Receptor-G Protein Coupling by Blocking Association of G Protein {alpha} and {beta}{gamma} Subunits
J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 191 - 198.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
D. Mielenz, C. Vettermann, M. Hampel, C. Lang, A. Avramidou, M. Karas, and H.-M. Jack
Lipid Rafts Associate with Intracellular B Cell Receptors and Exhibit a B Cell Stage-Specific Protein Composition
J. Immunol., March 15, 2005; 174(6): 3508 - 3517.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
E. L. Riddle, R. A. Schwartzman, M. Bond, and P. A. Insel
Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target?
Circ. Res., March 4, 2005; 96(4): 401 - 411.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
B. N. Armbruster and B. L. Roth
Mining the Receptorome
J. Biol. Chem., February 18, 2005; 280(7): 5129 - 5132.
[Full Text] [PDF]


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Eukaryot CellHome page
S. Krystofova and K. A. Borkovich
The Heterotrimeric G-Protein Subunits GNG-1 and GNB-1 Form a G{beta}{gamma} Dimer Required for Normal Female Fertility, Asexual Development, and G{alpha} Protein Levels in Neurospora crassa
Eukaryot. Cell, February 1, 2005; 4(2): 365 - 378.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
K. R. Kerchner, R. L. Clay, G. McCleery, N. Watson, W. E. McIntire, C.-S. Myung, and J. C. Garrison
Differential Sensitivity of Phosphatidylinositol 3-Kinase p110{gamma} to Isoforms of G Protein {beta}{gamma} Dimers
J. Biol. Chem., October 22, 2004; 279(43): 44554 - 44562.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
I. D. Alves, K. A. Ciano, V. Boguslavski, E. Varga, Z. Salamon, H. I. Yamamura, V. J. Hruby, and G. Tollin
Selectivity, Cooperativity, and Reciprocity in the Interactions between the {delta}-Opioid Receptor, Its Ligands, and G-proteins
J. Biol. Chem., October 22, 2004; 279(43): 44673 - 44682.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
L. Bogdanik, R. Mohrmann, A. Ramaekers, J. Bockaert, Y. Grau, K. Broadie, and M.-L. Parmentier
The Drosophila Metabotropic Glutamate Receptor DmGluRA Regulates Activity-Dependent Synaptic Facilitation and Fine Synaptic Morphology
J. Neurosci., October 13, 2004; 24(41): 9105 - 9116.
[Abstract] [Full Text] [PDF]


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Mol. Interv.Home page
M. B. Jones, D. P. Siderovski, and S. B. Hooks
The G{beta}{gamma} DIMER as a NOVEL SOURCE of SELECTIVITY in G-Protein Signaling: GGL-ing AT CONVENTION
Mol. Interv., August 1, 2004; 4(4): 200 - 214.
[Abstract] [Full Text] [PDF]


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Plant CellHome page
N. A. Eckardt
Abscisic Acid Signal Transduction: Function of G Protein-Coupled Receptor 1 in Arabidopsis
PLANT CELL, June 1, 2004; 16(6): 1353 - 1354.
[Full Text] [PDF]




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