scholarly journals Naturally-Occurring Mutation in the Calcium-Sensing Receptor Reveals the Significance of Extracellular Domain Loop III Region for Class C G Protein-Coupled Receptor Function

2010 ◽  
Vol 24 (8) ◽  
pp. 1676-1676
Author(s):  
Qing Dong ◽  
Zhiqiang Cheng ◽  
Wenhan Chang ◽  
Brigitte E. Blackman ◽  
Felix A. Conte ◽  
...  
Keyword(s):  
G Protein ◽  
Extracellular Domain ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Naturally Occurring ◽  
Class C ◽  
G Protein Coupled

scholarly journals Recent advances in understanding the extracellular calcium-sensing receptor

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2535 ◽  
Author(s):  
Matilde Colella ◽  
Andrea Gerbino ◽  
Aldebaran M. Hofer ◽  
Silvana Curci
Keyword(s):  
G Protein ◽  
Calcium Homeostasis ◽  
Body Fluids ◽  
Extracellular Calcium ◽  
G Protein Coupled Receptor ◽  
Calcium Sensing Receptor ◽  
Endogenous Ligands ◽  
Calcium Sensing ◽  
Intracellular Signals ◽  
G Protein Coupled

The extracellular calcium-sensing receptor (CaR), a ubiquitous class C G-protein-coupled receptor (GPCR), is responsible for the control of calcium homeostasis in body fluids. It integrates information about external Ca2+ and a surfeit of other endogenous ligands into multiple intracellular signals, but how is this achieved? This review will focus on some of the exciting concepts in CaR signaling and pharmacology that have emerged in the last few years.

scholarly journals Positive and Negative Allosteric Modulators Promote Biased Signaling at the Calcium-Sensing Receptor

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1232-1241 ◽  
Author(s):  
Anna E. Davey ◽  
Katie Leach ◽  
Celine Valant ◽  
Arthur D. Conigrave ◽  
Patrick M. Sexton ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
G Protein ◽  
Allosteric Modulators ◽  
G Protein Coupled Receptor ◽  
Calcium Sensing Receptor ◽  
Quantitative Evidence ◽  
Membrane Ruffling ◽  
Beneficial Effects ◽  
Calcium Sensing ◽  
G Protein Coupled

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor whose function can be allosterically modulated in a positive or negative manner by calcimimetics or calcilytics, respectively. Indeed, the second-generation calcimimetic, cinacalcet, has proven clinically useful in the treatment of chronic kidney disease patients with secondary hyperparathyroidism but is not widely used in earlier stages of renal disease due to the potential to predispose such patients to hypocalcaemia and hyperphosphatemia. The development of a biased CaSR ligand that is more selective for specific signaling pathway(s) leading only to beneficial effects may overcome this limitation. The detection of such stimulus-bias at a G protein-coupled receptor requires investigation across multiple signaling pathways and the development of methods to quantify the effects of allosteric ligands on orthosteric ligand affinity and cooperativity at each pathway. In the current study, we determined the effects of the calcimimetics, NPS-R568 or cinacalcet, and the calcilytic, NPS-2143, on Cao2+-mediated intracellular Ca2+ mobilization, ERK1/2 phosphorylation, and plasma membrane ruffling in a stably transfected human embryonic kidney 293-TREx c-myc-CaSR cell line and applied a novel analytical model to quantify these modulator effects. We present quantitative evidence for the generation of stimulus bias by both positive and negative allosteric modulators of the CaSR, manifested as greater allosteric modulation of intracellular Ca2+ mobilization relative to ERK1/2 phosphorylation, and a higher affinity of the modulators for the state of the CaSR mediating plasma membrane ruffling relative to the other two pathways. Our findings provide the first evidence that an allosteric modulator used in clinical practice exhibits stimulus bias.

scholarly journals Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function

2020 ◽  
Vol 45 (12) ◽  
pp. 1049-1064
Author(s):  
Amr Ellaithy ◽  
Javier Gonzalez-Maeso ◽  
Diomedes A. Logothetis ◽  
Joshua Levitz
Keyword(s):  
G Protein ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
Class C ◽  
G Protein Coupled

Rescue of Defective G Protein-Coupled Receptor Function by Intermolecular Cooperation

2013 ◽  
pp. 239-255 ◽  
Author(s):  
Ashutosh Trehan ◽  
Kim Carol Jonas ◽  
Ilpo Huhtaniemi ◽  
Aylin Carla Hanyaloglu ◽  
Adolfo Rivero-Müller
Keyword(s):  
G Protein ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Structural basis of G protein-coupled receptor function

1999 ◽  
Vol 151 (1-2) ◽  
pp. 181-193 ◽  
Author(s):  
Torsten Schöneberg ◽  
Günter Schultz ◽  
Thomas Gudermann
Keyword(s):  
G Protein ◽  
Structural Basis ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Roles of the G protein-coupled receptor kinase 2 and Rab5 in α1B-adrenergic receptor function and internalization

2020 ◽  
Vol 867 ◽  
pp. 172846
Author(s):  
David A. Hernández-Espinosa ◽  
Guadalupe Reyes-Cruz ◽  
J. Adolfo García-Sáinz
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Consequences of splice variation on Secretin family G protein-coupled receptor function

2012 ◽  
Vol 166 (1) ◽  
pp. 98-109 ◽  
Author(s):  
Sebastian GB Furness ◽  
Denise Wootten ◽  
Arthur Christopoulos ◽  
Patrick M Sexton
Keyword(s):  
G Protein ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
Splice Variation ◽  
G Protein Coupled
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