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β-Arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors
Mounia Azzi*,
Pascale G. Charest*,
Stéphane Angers*,
Guy Rousseau,
Trudy Kohout,
Michel Bouvier*,, and
Graciela Piñeyro¶
*Department of Biochemistry, Université de Montréal, Montréal, QC, Canada H3C 3J7; Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada HGJ 1C5; Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710; and ¶Département de Psychiatrie, Centre de Recherche Fernand-Seguin, Université de Montréal, Montréal, QC, Canada H1N 3V2
Received for publication November 1, 2002.
Abstract:
It is becoming increasingly clear that signaling via G protein-coupledreceptors is a diverse phenomenon involving receptor interactionwith a variety of signaling partners. Despite this diversity,receptor ligands are commonly classified only according to theirability to modify G protein-dependent signaling. Here we showthat β2AR ligands like ICI118551 and propranolol, whichare inverse agonists for Gs-stimulated adenylyl cyclase, inducepartial agonist responses for the mitogen-activated proteinkinases extracellular signal-regulated kinase (ERK) 1/2 thusbehaving as dual efficacy ligands. ERK1/2 activation by dualefficacy ligands was not affected by ADP-ribosylation of Gαiand could be observed in S49-cyc– cells lacking Gαsindicating that, unlike the conventional agonist isoproterenol,these drugs induce ERK1/2 activation in a Gs/i-independent manner.In contrast, this activation was inhibited by a dominant negativemutant of β-arrestin and was abolished in mouse embryonicfibroblasts lacking β-arrestin 1 and 2. The role of β-arrestinwas further confirmed by showing that transfection of β-arrestin2 in these knockout cells restored ICI118551 promoted ERK1/2activation. ICI118551 and propranolol also promoted β-arrestinrecruitment to the receptor. Taken together, these observationssuggest that β-arrestin recruitment is not an exclusiveproperty of agonists, and that ligands classically classifiedas inverse agonists rely exclusively on β-arrestin fortheir positive signaling activity. This phenomenon is not uniqueto β2-adrenergic ligands because SR121463B, an inverseagonist on the V2 vasopressin receptor-stimulated adenylyl cyclase,recruited β-arrestin and stimulated ERK1/2. These resultspoint to a multistate model of receptor activation in whichligand-specific conformations are capable of differentiallyactivating distinct signaling partners.
To whom correspondence should be addressed. E-mail: michel.bouvier{at}umontreal.ca.
Edited by Robert J. Lefkowitz, Duke University Medical Center,Durham, NC, and approved July 22, 2003
This paper was submitted directly (Track II) to the PNAS office.
A G Protein-Biased Ligand at the {mu}-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine.
S. M. DeWire, D. S. Yamashita, D. H. Rominger, G. Liu, C. L. Cowan, T. M. Graczyk, X.-T. Chen, P. M. Pitis, D. Gotchev, C. Yuan, et al. (2013)
J. Pharmacol. Exp. Ther.
344, 708-717
|Abstract »|Full Text »|PDF »
Regulation of {micro}-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance.
J. T. Williams, S. L. Ingram, G. Henderson, C. Chavkin, M. von Zastrow, S. Schulz, T. Koch, C. J. Evans, and M. J. Christie (2013)
Pharmacol. Rev.
65, 223-254
|Abstract »|Full Text »|PDF »
Induction of Cardiac Fibrosis by {beta}-Blocker in G Protein-independent and G Protein-coupled Receptor Kinase 5/{beta}-Arrestin2-dependent Signaling Pathways.
M. Nakaya, S. Chikura, K. Watari, N. Mizuno, K. Mochinaga, S. Mangmool, S. Koyanagi, S. Ohdo, Y. Sato, T. Ide, et al. (2012)
J. Biol. Chem.
287, 35669-35677
|Abstract »|Full Text »|PDF »
Discovery of Regulators of Receptor Internalization with High-Throughput Flow Cytometry.
Y. Wu, P. H. Tapia, G. W. Fisher, P. C. Simons, J. J. Strouse, T. Foutz, A. S. Waggoner, J. Jarvik, and L. A. Sklar (2012)
Mol. Pharmacol.
82, 645-657
|Abstract »|Full Text »|PDF »
Casting a Wider Net: Whole-Cell Assays to Capture Varied and Biased Signaling.
Identification and Characterization of an Activating F229V Substitution in the V2 Vasopressin Receptor in an Infant with NSIAD.
E. Carpentier, L. A. Greenbaum, D. Rochdi, R. Abrol, W. A. Goddard III, D. G. Bichet, and M. Bouvier (2012)
J. Am. Soc. Nephrol.
23, 1635-1640
|Abstract »|Full Text »|PDF »
Silent Scaffolds: INHIBITION OF c-Jun N-TERMINAL KINASE 3 ACTIVITY IN CELL BY DOMINANT-NEGATIVE ARRESTIN-3 MUTANT.
M. Breitman, S. Kook, L. E. Gimenez, B. N. Lizama, M. C. Palazzo, E. V. Gurevich, and V. V. Gurevich (2012)
J. Biol. Chem.
287, 19653-19664
|Abstract »|Full Text »|PDF »
Differential {beta}-Arrestin-Dependent Conformational Signaling and Cellular Responses Revealed by Angiotensin Analogs.
B. Zimmerman, A. Beautrait, B. Aguila, R. Charles, E. Escher, A. Claing, M. Bouvier, and S. A. Laporte (2012)
Science Signaling
5, ra33
|Abstract »|Full Text »|PDF »
Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy.
R. Rahmeh, M. Damian, M. Cottet, H. Orcel, C. Mendre, T. Durroux, K. S. Sharma, G. Durand, B. Pucci, E. Trinquet, et al. (2012)
PNAS
109, 6733-6738
|Abstract »|Full Text »|PDF »
Differential Association of Receptor-G{beta}{gamma} Complexes with {beta}-Arrestin2 Determines Recycling Bias and Potential for Tolerance of Delta Opioid Receptor Agonists.
N. Audet, I. Charfi, O. Mnie-Filali, M. Amraei, A.-J. Chabot-Dore, M. Millecamps, L. S. Stone, and G. Pineyro (2012)
J. Neurosci.
32, 4827-4840
|Abstract »|Full Text »|PDF »
Fluorescence/Bioluminescence Resonance Energy Transfer Techniques to Study G-Protein-Coupled Receptor Activation and Signaling.
Functional Selective Oxytocin-derived Agonists Discriminate between Individual G Protein Family Subtypes.
M. Busnelli, A. Sauliere, M. Manning, M. Bouvier, C. Gales, and B. Chini (2012)
J. Biol. Chem.
287, 3617-3629
|Abstract »|Full Text »|PDF »
V2 Vasopressin Receptor (V2R) Mutations in Partial Nephrogenic Diabetes Insipidus Highlight Protean Agonism of V2R Antagonists.
K. Takahashi, N. Makita, K. Manaka, M. Hisano, Y. Akioka, K. Miura, N. Takubo, A. Iida, N. Ueda, M. Hashimoto, et al. (2012)
J. Biol. Chem.
287, 2099-2106
|Abstract »|Full Text »|PDF »
Nuclear GPCRs in cardiomyocytes: an insider's view of {beta}-adrenergic receptor signaling.
G. Vaniotis, B. G. Allen, and T. E. Hebert (2011)
Am J Physiol Heart Circ Physiol
301, H1754-H1764
|Abstract »|Full Text »|PDF »
CXCR7/CXCR4 Heterodimer Constitutively Recruits {beta}-Arrestin to Enhance Cell Migration.
F. M. Decaillot, M. A. Kazmi, Y. Lin, S. Ray-Saha, T. P. Sakmar, and P. Sachdev (2011)
J. Biol. Chem.
286, 32188-32197
|Abstract »|Full Text »|PDF »
Ligand Modulation of the Epstein-Barr Virus-induced Seven-transmembrane Receptor EBI2: IDENTIFICATION OF A POTENT AND EFFICACIOUS INVERSE AGONIST.
T. Benned-Jensen, C. Smethurst, P. J. Holst, K. R. Page, H. Sauls, B. Sivertsen, T. W. Schwartz, A. Blanchard, R. Jepras, and M. M. Rosenkilde (2011)
J. Biol. Chem.
286, 29292-29302
|Abstract »|Full Text »|PDF »
Unique Interaction Pattern for a Functionally Biased Ghrelin Receptor Agonist.
B. Sivertsen, M. Lang, T. M. Frimurer, N. D. Holliday, A. Bach, S. Els, M. S. Engelstoft, P. S. Petersen, A. N. Madsen, T. W. Schwartz, et al. (2011)
J. Biol. Chem.
286, 20845-20860
|Abstract »|Full Text »|PDF »
Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of {beta}-arrestin2.
C. Yin, R. Zhang, Y. Xu, Q. Chen, and X. Xie (2011)
Mol. Biol. Cell
22, 1608-1616
|Abstract »|Full Text »|PDF »
Nuclear Factor {kappa}B Downregulates the Transient Outward Potassium Current Ito,f Through Control of KChIP2 Expression.
B. K. Panama, D. Latour-Villamil, G. P. Farman, D. Zhao, S.-S. Bolz, L. A. Kirshenbaum, and P. H. Backx (2011)
Circ. Res.
108, 537-543
|Abstract »|Full Text »|PDF »
Functional Selectivity and Biased Receptor Signaling.
Serine 363 of the {delta}-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands.
C. Xu, M.-H. Hong, L.-S. Zhang, Y.-Y. Hou, Y.-H. Wang, F.-F. Wang, Y.-J. Chen, X.-J. Xu, J. Chen, X. Xie, et al. (2010)
J. Cell Sci.
123, 4259-4270
|Abstract »|Full Text »|PDF »
{beta}-Blocker drugs mediate calcium signaling in native central nervous system neurons by {beta}-arrestin-biased agonism.
A. V. Tzingounis, M. von Zastrow, and G. A. Yudowski (2010)
PNAS
107, 21028-21033
|Abstract »|Full Text »|PDF »
Allostery at G Protein-Coupled Receptor Homo- and Heteromers: Uncharted Pharmacological Landscapes.
P. Molinari, V. Vezzi, M. Sbraccia, C. Gro, D. Riitano, C. Ambrosio, I. Casella, and T. Costa (2010)
J. Biol. Chem.
285, 12522-12535
|Abstract »|Full Text »|PDF »
The Constitutive Activity of the Human Muscarinic M3 Receptor Unmasks Differences in the Pharmacology of Anticholinergics.
P. Casarosa, T. Kiechle, P. Sieger, M. Pieper, and F. Gantner (2010)
J. Pharmacol. Exp. Ther.
333, 201-209
|Abstract »|Full Text »|PDF »
Partially Deglycosylated Equine LH Preferentially Activates {beta}-Arrestin-Dependent Signaling at the Follicle-Stimulating Hormone Receptor.
V. Wehbi, T. Tranchant, G. Durand, A. Musnier, J. Decourtye, V. Piketty, V. Y. Butnev, G. R. Bousfield, P. Crepieux, M.-C. Maurel, et al. (2010)
Mol. Endocrinol.
24, 561-573
|Abstract »|Full Text »|PDF »
Ligand- and Heterodimer-Directed Signaling of the CB1 Cannabinoid Receptor.
B. D. Hudson, T. E. Hebert, and M. E. M. Kelly (2010)
Mol. Pharmacol.
77, 1-9
|Abstract »|Full Text »|PDF »
Biased Agonist Pharmacochaperones of the AVP V2 Receptor May Treat Congenital Nephrogenic Diabetes Insipidus.
F. Jean-Alphonse, S. Perkovska, M.-C. Frantz, T. Durroux, C. Mejean, D. Morin, S. Loison, D. Bonnet, M. Hibert, B. Mouillac, et al. (2009)
J. Am. Soc. Nephrol.
20, 2190-2203
|Abstract »|Full Text »|PDF »
Activation of Intracellular Signaling Pathways by the Murine Cytomegalovirus G Protein-Coupled Receptor M33 Occurs via PLC-{beta}/PKC-Dependent and -Independent Mechanisms.
J. D. Sherrill, M. P. Stropes, O. D. Schneider, D. E. Koch, F. M. Bittencourt, J. L. C. Miller, and W. E. Miller (2009)
J. Virol.
83, 8141-8152
|Abstract »|Full Text »|PDF »
The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex.
X. J. Yao, G. Velez Ruiz, M. R. Whorton, S. G. F. Rasmussen, B. T. DeVree, X. Deupi, R. K. Sunahara, and B. Kobilka (2009)
PNAS
106, 9501-9506
|Abstract »|Full Text »|PDF »
Evidence for Distinct Antagonist-Revealed Functional States of 5-Hydroxytryptamine2A Receptor Homodimers.
J. Brea, M. Castro, J. Giraldo, J. F. Lopez-Gimenez, J. F. Padin, F. Quintian, M. I. Cadavid, M. T. Vilaro, G. Mengod, K. A. Berg, et al. (2009)
Mol. Pharmacol.
75, 1380-1391
|Abstract »|Full Text »|PDF »
Hematopoietic Protein Tyrosine Phosphatase Mediates {beta}2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes.
The C-terminal Tail of CRTH2 Is a Key Molecular Determinant That Constrains G{alpha}i and Downstream Signaling Cascade Activation.
R. Schroder, N. Merten, J. M. Mathiesen, L. Martini, A. Kruljac-Letunic, F. Krop, A. Blaukat, Y. Fang, E. Tran, T. Ulven, et al. (2009)
J. Biol. Chem.
284, 1324-1336
|Abstract »|Full Text »|PDF »
.
M. Sato, D. S. Hutchinson, B. A. Evans, and R. J. Summers (2008)
Mol. Pharmacol.
74, 1417-1428
|Abstract »|Full Text »|PDF »
Physical Interaction of Calmodulin with the 5-Hydroxytryptamine2C Receptor C-Terminus Is Essential for G Protein-independent, Arrestin-dependent Receptor Signaling.
M. Labasque, E. Reiter, C. Becamel, J. Bockaert, and P. Marin (2008)
Mol. Biol. Cell
19, 4640-4650
|Abstract »|Full Text »|PDF »
Site-specific Cleavage of G Protein-coupled Receptor-engaged {beta}-Arrestin: INFLUENCE OF THE AT1 RECEPTOR CONFORMATION ON SCISSILE SITE SELECTION.
C. Lee, S. Bhatt, A. Shukla, R. W. Desnoyer, S. P. Yadav, M. Kim, S.-H. Jang, and S. S. Karnik (2008)
J. Biol. Chem.
283, 21612-21620
|Abstract »|Full Text »|PDF »
Distinct conformational changes in {beta}-arrestin report biased agonism at seven-transmembrane receptors.
A. K. Shukla, J. D. Violin, E. J. Whalen, D. Gesty-Palmer, S. K. Shenoy, and R. J. Lefkowitz (2008)
PNAS
105, 9988-9993
|Abstract »|Full Text »|PDF »
Agonist-selective signaling is determined by the receptor location within the membrane domains.
H. Zheng, J. Chu, Y. Qiu, H. H. Loh, and P.-Y. Law (2008)
PNAS
105, 9421-9426
|Abstract »|Full Text »|PDF »
Bioluminescence Resonance Energy Transfer Assays Reveal Ligand-specific Conformational Changes within Preformed Signaling Complexes Containing {delta}-Opioid Receptors and Heterotrimeric G Proteins.
N. Audet, C. Gales, E. Archer-Lahlou, M. Vallieres, P. W. Schiller, M. Bouvier, and G. Pineyro (2008)
J. Biol. Chem.
283, 15078-15088
|Abstract »|Full Text »|PDF »
Agonist-occupied A3 adenosine receptors exist within heterogeneous complexes in membrane microdomains of individual living cells.
Y. Cordeaux, S. J. Briddon, S. P. H. Alexander, B. Kellam, and S. J. Hill (2008)
FASEB J
22, 850-860
|Abstract »|Full Text »|PDF »
{beta}-Arrestin-biased Agonism at the {beta}2-Adrenergic Receptor.
M. T. Drake, J. D. Violin, E. J. Whalen, J. W. Wisler, S. K. Shenoy, and R. J. Lefkowitz (2008)
J. Biol. Chem.
283, 5669-5676
|Abstract »|Full Text »|PDF »
Role of -Arrestin-mediated Desensitization and Signaling in the Control of Angiotensin AT1a Receptor-stimulated Transcription.
M.-H. Lee, H. M. El-Shewy, D. K. Luttrell, and L. M. Luttrell (2008)
J. Biol. Chem.
283, 2088-2097
|Abstract »|Full Text »|PDF »
Norepinephrine- and Epinephrine-induced Distinct 2-Adrenoceptor Signaling Is Dictated by GRK2 Phosphorylation in Cardiomyocytes.
Y. Wang, V. De Arcangelis, X. Gao, B. Ramani, Y.-s. Jung, and Y. Xiang (2008)
J. Biol. Chem.
283, 1799-1807
|Abstract »|Full Text »|PDF »
-Arrestin-Dependent {micro}-Opioid Receptor-Activated Extracellular Signal-Regulated Kinases (ERKs) Translocate to Nucleus in Contrast to G Protein-Dependent ERK Activation.
Ligand-Directed Signaling at the beta3-Adrenoceptor Produced by 3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate (SR59230A) Relative to Receptor Agonists.
M. Sato, T. Horinouchi, D. S. Hutchinson, B. A. Evans, and R. J. Summers (2007)
Mol. Pharmacol.
72, 1359-1368
|Abstract »|Full Text »|PDF »
Quantification of dynamic protein complexes using Renilla luciferase fragment complementation applied to protein kinase A activities in vivo.
E. Stefan, S. Aquin, N. Berger, C. R. Landry, B. Nyfeler, M. Bouvier, and S. W. Michnick (2007)
PNAS
104, 16916-16921
|Abstract »|Full Text »|PDF »
A unique mechanism of beta-blocker action: Carvedilol stimulates beta-arrestin signaling.
J. W. Wisler, S. M. DeWire, E. J. Whalen, J. D. Violin, M. T. Drake, S. Ahn, S. K. Shenoy, and R. J. Lefkowitz (2007)
PNAS
104, 16657-16662
|Abstract »|Full Text »|PDF »
{beta}-Arrestin-Dependent Parathyroid Hormone-Stimulated Extracellular Signal-Regulated Kinase Activation and Parathyroid Hormone Type 1 Receptor Internalization.
G-protein-coupled receptor expression, function, and signaling in macrophages.
J. Lattin, D. A. Zidar, K. Schroder, S. Kellie, D. A. Hume, and M. J. Sweet (2007)
J. Leukoc. Biol.
82, 16-32
|Abstract »|Full Text »|PDF »
Structure and Conformational Changes in the C-terminal Domain of the beta2-Adrenoceptor: INSIGHTS FROM FLUORESCENCE RESONANCE ENERGY TRANSFER STUDIES.
S. Granier, S. Kim, A. M. Shafer, V. R. P. Ratnala, J. J. Fung, R. N. Zare, and B. Kobilka (2007)
J. Biol. Chem.
282, 13895-13905
|Abstract »|Full Text »|PDF »
Protean Agonism at the Dopamine D2 Receptor: (S)-3-(3-Hydroxyphenyl)-N-propylpiperidine Is an Agonist for Activation of Go1 but an Antagonist/Inverse Agonist for Gi1,Gi2, and Gi3.
J. R. Lane, B. Powney, A. Wise, S. Rees, and G. Milligan (2007)
Mol. Pharmacol.
71, 1349-1359
|Abstract »|Full Text »|PDF »
An acquired hypocalciuric hypercalcemia autoantibody induces allosteric transition among active human Ca-sensing receptor conformations.
N. Makita, J. Sato, K. Manaka, Y. Shoji, A. Oishi, M. Hashimoto, T. Fujita, and T. Iiri (2007)
PNAS
104, 5443-5448
|Abstract »|Full Text »|PDF »
Bioluminescence Resonance Energy Transfer as a Screening Assay: Focus on Partial and Inverse Agonism.
L. Elster, C. Elling, and A. Heding (2007)
J Biomol Screen
12, 41-49
|Abstract »|PDF »
Proline-rich Motifs in the Parathyroid Hormone (PTH)/PTH-related Protein Receptor C Terminus Mediate Scaffolding of c-Src with beta-Arrestin2 for ERK1/2 Activation.
A. Rey, D. Manen, R. Rizzoli, J. Caverzasio, and S. L. Ferrari (2006)
J. Biol. Chem.
281, 38181-38188
|Abstract »|Full Text »|PDF »
The Natural Inverse Agonist Agouti-related Protein Induces Arrestin-mediated Endocytosis of Melanocortin-3 and -4 Receptors.
A. Breit, K. Wolff, H. Kalwa, H. Jarry, T. Buch, and T. Gudermann (2006)
J. Biol. Chem.
281, 37447-37456
|Abstract »|Full Text »|PDF »
Activation of STAT3 by G{alpha}s Distinctively Requires Protein Kinase A, JNK, and Phosphatidylinositol 3-Kinase.
A. M. F. Liu, R. K. H. Lo, C. S. S. Wong, C. Morris, H. Wise, and Y. H. Wong (2006)
J. Biol. Chem.
281, 35812-35825
|Abstract »|Full Text »|PDF »
Distinct Signaling Profiles of beta1 and beta2 Adrenergic Receptor Ligands toward Adenylyl Cyclase and Mitogen-Activated Protein Kinase Reveals the Pluridimensionality of Efficacy.
beta-Arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes.
K. Rajagopal, E. J. Whalen, J. D. Violin, J. A. Stiber, P. B. Rosenberg, R. T. Premont, T. M. Coffman, H. A. Rockman, and R. J. Lefkowitz (2006)
PNAS
103, 16284-16289
|Abstract »|Full Text »|PDF »
G protein-coupled receptor kinase 2 and {beta}-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells.
S. Marion, E. Kara, P. Crepieux, V. Piketty, N. Martinat, F. Guillou, and E. Reiter (2006)
J. Endocrinol.
190, 341-350
|Abstract »|Full Text »|PDF »
G-protein-coupled Receptor Kinase Specificity for beta-Arrestin Recruitment to the beta2-Adrenergic Receptor Revealed by Fluorescence Resonance Energy Transfer.
J. D. Violin, X.-R. Ren, and R. J. Lefkowitz (2006)
J. Biol. Chem.
281, 20577-20588
|Abstract »|Full Text »|PDF »
Constitutive ERK1/2 Activation by a Chimeric Neurokinin 1 Receptor-beta-Arrestin1 Fusion Protein: PROBING THE COMPOSITION AND FUNCTION OF THE G PROTEIN-COUPLED RECEPTOR "SIGNALSOME".
F. Jafri, H. M. El-Shewy, M.-H. Lee, M. Kelly, D. K. Luttrell, and L. M. Luttrell (2006)
J. Biol. Chem.
281, 19346-19357
|Abstract »|Full Text »|PDF »
Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1 channels in living cells.
R. V. Rebois, M. Robitaille, C. Gales, D. J. Dupre, A. Baragli, P. Trieu, N. Ethier, M. Bouvier, and T. E. Hebert (2006)
J. Cell Sci.
119, 2807-2818
|Abstract »|Full Text »|PDF »
Distinct beta-Arrestin- and G Protein-dependent Pathways for Parathyroid Hormone Receptor-stimulated ERK1/2 Activation.
D. Gesty-Palmer, M. Chen, E. Reiter, S. Ahn, C. D. Nelson, S. Wang, A. E. Eckhardt, C. L. Cowan, R. F. Spurney, L. M. Luttrell, et al. (2006)
J. Biol. Chem.
281, 10856-10864
|Abstract »|Full Text »|PDF »
Evidence for a Secondary State of the Human {beta}3-Adrenoceptor.
Characterization of Isoprenaline- and Salmeterol-Stimulated Interactions between {beta}2-Adrenoceptors and {beta}-Arrestin 2 Using {beta}-Galactosidase Complementation in C2C12 Cells.
{beta}-Arrestin 2 Expression Determines the Transcriptional Response to Lysophosphatidic Acid Stimulation in Murine Embryo Fibroblasts.
D. Gesty-Palmer, H. E. Shewy, T. A. Kohout, and L. M. Luttrell (2005)
J. Biol. Chem.
280, 32157-32167
|Abstract »|Full Text »|PDF »
The Origins of Diversity and Specificity in G Protein-Coupled Receptor Signaling.
S. Maudsley, B. Martin, and L. M. Luttrell (2005)
J. Pharmacol. Exp. Ther.
314, 485-494
|Abstract »|Full Text »|PDF »
Identification of Indole Derivatives Exclusively Interfering with a G Protein-Independent Signaling Pathway of the Prostaglandin D2 Receptor CRTH2.
J. M. Mathiesen, T. Ulven, L. Martini, L. O. Gerlach, A. Heinemann, and E. Kostenis (2005)
Mol. Pharmacol.
68, 393-402
|Abstract »|Full Text »|PDF »
Probing the {beta}2 Adrenoceptor Binding Site with Catechol Reveals Differences in Binding and Activation by Agonists and Partial Agonists.
G. Swaminath, X. Deupi, T. W. Lee, W. Zhu, F. S. Thian, T. S. Kobilka, and B. Kobilka (2005)
J. Biol. Chem.
280, 22165-22171
|Abstract »|Full Text »|PDF »
Multiple Signaling States of G-Protein-Coupled Receptors.
Mutation of the DRY Motif Reveals Different Structural Requirements for the CC Chemokine Receptor 5-Mediated Signaling and Receptor Endocytosis.
B. Lagane, S. Ballet, T. Planchenault, K. Balabanian, E. Le Poul, C. Blanpain, Y. Percherancier, I. Staropoli, G. Vassart, M. Oppermann, et al. (2005)
Mol. Pharmacol.
67, 1966-1976
|Abstract »|Full Text »|PDF »
Transduction of Receptor Signals by {beta}-Arrestins.
The Oxytocin Receptor Antagonist Atosiban Inhibits Cell Growth via a "Biased Agonist" Mechanism.
A. Reversi, V. Rimoldi, T. Marrocco, P. Cassoni, G. Bussolati, M. Parenti, and B. Chini (2005)
J. Biol. Chem.
280, 16311-16318
|Abstract »|Full Text »|PDF »
The Natural Mutation Encoding a C Terminus-Truncated 5-Hydroxytryptamine2B Receptor Is a Gain of Proliferative Functions.
M. Deraet, P. Manivet, A. Janoshazi, J. Callebert, S. Guenther, L. Drouet, J.-M. Launay, and L. Maroteaux (2005)
Mol. Pharmacol.
67, 983-991
|Abstract »|Full Text »|PDF »
Internalization and Src Activity Regulate the Time Course of ERK Activation by Delta Opioid Receptor Ligands.
N. Audet, M. Paquin-Gobeil, O. Landry-Paquet, P. W. Schiller, and G. Pineyro (2005)
J. Biol. Chem.
280, 7808-7816
|Abstract »|Full Text »|PDF »
Different G protein-coupled receptor kinases govern G protein and {beta}-arrestin-mediated signaling of V2 vasopressin receptor.
X.-R. Ren, E. Reiter, S. Ahn, J. Kim, W. Chen, and R. J. Lefkowitz (2005)
PNAS
102, 1448-1453
|Abstract »|Full Text »|PDF »
Reciprocal Regulation of Agonist and Inverse Agonist Signaling Efficacy upon Short-Term Treatment of the Human {delta}-Opioid Receptor with an Inverse Agonist.
G. Pineyro, M. Azzi, A. deLean, P. W. Schiller, and M. Bouvier (2005)
Mol. Pharmacol.
67, 336-348
|Abstract »|Full Text »|PDF »
Differential Desensitization, Receptor Phosphorylation, {beta}-Arrestin Recruitment, and ERK1/2 Activation by the Two Endogenous Ligands for the CC Chemokine Receptor 7.
T. A. Kohout, S. L. Nicholas, S. J. Perry, G. Reinhart, S. Junger, and R. S. Struthers (2004)
J. Biol. Chem.
279, 23214-23222
|Abstract »|Full Text »|PDF »
Agonist Binding: A Multistep Process.
B. Kobilka (2004)
Mol. Pharmacol.
65, 1060-1062
|Full Text »
Inverse Agonists: Tools to Reveal Ligand-Specific Conformations of G Protein-Coupled Receptors.
To whom correspondence should be addressed. E-mail: michel.bouvier{at}umontreal.ca. 
,
Trudy Kohout
,
Michel Bouvier*,
, and
Graciela Piñeyro¶
