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1

Tibrewal, Richa, Reynoldly Kharsyntiew, Farida Dawood, and Archana Sharma. "A REVIEW ON G-PROTEIN COUPLED RECEPTOR." International Journal of Current Pharmaceutical Review and Research 13, no. 04 (2021): 01–09. https://doi.org/10.5281/zenodo.12664417.

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AbstractG protein–coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domainreceptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein–linkedreceptors (GPLR), constitute a large protein family of receptors that detect molecules outsidethe cell and activate internal signal transduction pathways and, ultimately, cellular responses.Coupling with G proteins, they are called seven-transmembrane receptors because they passthrough the cell membrane seven times. G protein–coupled receptors are found only ineukaryotes, including yeast, choanof
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2

Sulon, Sarah M., and Jeffrey L. Benovic. "Targeting G protein–coupled receptor kinases to G protein–coupled receptors." Current Opinion in Endocrine and Metabolic Research 16 (February 2021): 56–65. http://dx.doi.org/10.1016/j.coemr.2020.09.002.

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3

Zeng, Fu-Yue. "Signaling by G Protein-Coupled Receptors." Electronic Journal of Pathology and Histology 6, no. 1 (2000): 13. https://doi.org/10.3233/eph-2000-6_1_13.

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G protein-coupled receptors represent one of the largest families of cell surface receptors in nature. These receptors play fundamental roles in diverse physiological processes such as neurotransmission, cellular metabolism, cell differentiation and growth as well as immune response. In response to extracellular ligands, G protein-coupled receptors specifically interact with heterotrimeric G proteins that can then activate or inhibit effector enzymes, ultimately leading to the physiological response. Biochemical and mutational studies have revealed the molecular mechanisms of ligand-receptor i
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4

Hille, Bertil. "G protein-coupled receptor." Scholarpedia 4, no. 12 (2009): 8214. http://dx.doi.org/10.4249/scholarpedia.8214.

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5

Milligan, G. "Oligomerisation of G-protein-coupled receptors." Journal of Cell Science 114, no. 7 (2001): 1265–71. http://dx.doi.org/10.1242/jcs.114.7.1265.

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A range of approaches have recently provided evidence that G-protein-coupled receptors can exist as oligomeric complexes. Both homo-oligomers, comprising multiple copies of the same gene product, and hetero-oligomers containing more than one receptor have been detected. In several, but not all, examples, the extent of oligomerisation is regulated by the presence of agonist ligands, and emerging evidence indicates that receptor hetero-oligomers can display distinct pharmacological characteristics. A chaperonin-like role for receptor oligomerisation in effective delivery of newly synthesised rec
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6

Gomes, Ivone, Mohammed Akli Ayoub, Wakako Fujita, Werner C. Jaeger, Kevin D. G. Pfleger, and Lakshmi A. Devi. "G Protein–Coupled Receptor Heteromers." Annual Review of Pharmacology and Toxicology 56, no. 1 (2016): 403–25. http://dx.doi.org/10.1146/annurev-pharmtox-011613-135952.

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7

A.C., Hanyaloglu, Kroeger K.M., and Eidne K.A. "G-Protein Coupled Receptor Oligomerization." Pharmaceutical News 9, no. 5 (2002): 317–25. http://dx.doi.org/10.1080/10718940216626.

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8

Pitcher, Julie A., Neil J. Freedman, and Robert J. Lefkowitz. "G PROTEIN–COUPLED RECEPTOR KINASES." Annual Review of Biochemistry 67, no. 1 (1998): 653–92. http://dx.doi.org/10.1146/annurev.biochem.67.1.653.

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9

Palczewski, Krzysztof. "G Protein–Coupled Receptor Rhodopsin." Annual Review of Biochemistry 75, no. 1 (2006): 743–67. http://dx.doi.org/10.1146/annurev.biochem.75.103004.142743.

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10

Lohse, Martin J., Cornelius Krasel, Rainer Winstel, and Federico Mayor. "G-protein-coupled receptor kinases." Kidney International 49, no. 4 (1996): 1047–52. http://dx.doi.org/10.1038/ki.1996.153.

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11

Prossnitz, Eric R. "G protein-coupled estrogen receptor." Critical Care Medicine 40, no. 12 (2012): 3323–25. http://dx.doi.org/10.1097/ccm.0b013e31826be998.

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12

Civelli, Olivier, Rainer K. Reinscheid, Yan Zhang, Zhiwei Wang, Robert Fredriksson, and Helgi B. Schiöth. "G Protein–Coupled Receptor Deorphanizations." Annual Review of Pharmacology and Toxicology 53, no. 1 (2013): 127–46. http://dx.doi.org/10.1146/annurev-pharmtox-010611-134548.

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13

Lefkowitz, Robert J. "G protein—coupled receptor kinases." Cell 74, no. 3 (1993): 409–12. http://dx.doi.org/10.1016/0092-8674(93)80042-d.

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14

Yeagle, Philip L., and Arlene D. Albert. "G-protein coupled receptor structure." Biochimica et Biophysica Acta (BBA) - Biomembranes 1768, no. 4 (2007): 808–24. http://dx.doi.org/10.1016/j.bbamem.2006.10.002.

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15

Palczewskl, Krzvsztof, and Jeffrey L. Benovic. "G-protein-coupled receptor kinases." Trends in Biochemical Sciences 16 (January 1991): 387–91. http://dx.doi.org/10.1016/0968-0004(91)90157-q.

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16

Rana, Brinda K., and Paul A. Insel. "G-protein-coupled receptor websites." Trends in Pharmacological Sciences 23, no. 11 (2002): 535–36. http://dx.doi.org/10.1016/s0165-6147(02)02113-2.

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17

Haga, Tatsuya, Kazuko Haga, and Kimihiko Kameyama. "G Protein-Coupled Receptor Kinases." Journal of Neurochemistry 63, no. 2 (2002): 400–412. http://dx.doi.org/10.1046/j.1471-4159.1994.63020400.x.

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18

Breitwieser, Gerda E. "G Protein–Coupled Receptor Oligomerization." Circulation Research 94, no. 1 (2004): 17–27. http://dx.doi.org/10.1161/01.res.0000110420.68526.19.

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19

Irani, Kaikobad. "G Protein–Coupled Receptor G2A." Circulation Research 100, no. 4 (2007): 450–51. http://dx.doi.org/10.1161/01.res.0000260274.62236.8f.

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20

Kerlavage, Anthony R. "G-protein-coupled receptor family." Current Opinion in Structural Biology 1, no. 3 (1991): 394–401. http://dx.doi.org/10.1016/0959-440x(91)90037-t.

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21

Fang, Ye, Anthony G. Frutos, and Joydeep Lahiri. "G-Protein-Coupled Receptor Microarrays." ChemBioChem 3, no. 10 (2002): 987–91. http://dx.doi.org/10.1002/1439-7633(20021004)3:10<987::aid-cbic987>3.0.co;2-m.

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22

Ferguson, SSG, L. S. Barak, J. Zhang, and M. G. Caron. "G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins." Canadian Journal of Physiology and Pharmacology 74, no. 10 (1996): 1095–110. http://dx.doi.org/10.1139/y96-124.

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23

Ferguson, S. S. G., J. Zhang, L. S. Barak, and M. G. Caron. "G-protein-coupled receptor kinases and arrestins: regulators of G-protein-coupled receptor sequestration." Biochemical Society Transactions 24, no. 4 (1996): 953–59. http://dx.doi.org/10.1042/bst0240953.

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24

Brann, Mark R., Terri Messier, Christine Dorman, and Deborah Lannigan. "Cell-Based Assays for G-Protein-Coupled/Tyrosine Kinase-Coupled Receptors." Journal of Biomolecular Screening 1, no. 1 (1996): 43–45. http://dx.doi.org/10.1177/108705719600100114.

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Using mammalian cells transiently transfected with receptors, we have developed an assay [Receptor Selection and Amplification Technology (R-SAT); patents pending] that links ligand-dependent cellular transformation to induction of 8-galactosidase in a 96-well plate format. Using these procedures, we have performed high throughput functional assays of receptors that mediate signal transduction by a diversity of mechanisms. Examples include the prostanoid, muscarinic, and neurokinin receptor subtypes that signal via the G-proteins Gq and Gi, the JAK/STAT-linked GM-CSF receptor, the tyrosine kin
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25

Shpakov, Alexander. "Allosteric Modulators of G Protein-Coupled Receptors." International Journal of Molecular Sciences 23, no. 6 (2022): 2934. http://dx.doi.org/10.3390/ijms23062934.

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26

Mayor, Federico. "G Protein-Coupled Receptor Kinases Take Central Stage." Cells 12, no. 1 (2022): 23. http://dx.doi.org/10.3390/cells12010023.

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The relevance of the family of G protein-coupled receptor kinases (GRKs) is based on its key participation in the regulation and intracellular dynamics of the largest family of membrane receptors, namely G protein-coupled receptors (GPCRs) [...]
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27

Harris, Raymond C. "EGF receptor activation by G-protein coupled receptors." Kidney International 58, no. 2 (2000): 898–99. http://dx.doi.org/10.1046/j.1523-1755.2000.00240.x.

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28

Li, Lingyong, Kristoff T. Homan, Sergey A. Vishnivetskiy, et al. "G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs)." Journal of Biological Chemistry 290, no. 17 (2015): 10775–90. http://dx.doi.org/10.1074/jbc.m115.644773.

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29

Thompson, Dawn, Margareta Pusch, and Jennifer L. Whistler. "Changes in G Protein-coupled Receptor Sorting Protein Affinity Regulate Postendocytic Targeting of G Protein-coupled Receptors." Journal of Biological Chemistry 282, no. 40 (2007): 29178–85. http://dx.doi.org/10.1074/jbc.m704014200.

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30

Prado, M. A., B. Evans-Bain, and I. M. Dickerson. "Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction." Biochemical Society Transactions 30, no. 4 (2002): 460–64. http://dx.doi.org/10.1042/bst0300460.

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The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1).CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling
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31

Parker, E. M., and D. W. Smith. "G Protein-Coupled Serotonin Receptors-Multiple Subtypes, Multiple Opportunities." Current Pharmaceutical Design 1, no. 3 (1995): 363–72. http://dx.doi.org/10.2174/1381612801666220918170118.

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Serotonin receptors have been fertile targets for drug development for decades. The attractiveness of serotonin receptors as drug targets is due to the wide range of physiological processes in which serotonin plays a role and to diversity of receptor subtypes that mediate the physiological effects of serotonin. The powerful combination of molecular cloning and pharmacology has thus far led to the identification of fifteen different serotonin receptor subtypes. Fourteen of these serotonin receptors are G protein­ coupled receptors and one is a ligand-gated ion channel. Because many of these ser
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32

Haga, Tatsuya. "G protein—coupled receptor kinase (GRK)." Folia Pharmacologica Japonica 136, no. 4 (2010): 215–18. http://dx.doi.org/10.1254/fpj.136.215.

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33

Schneider, L. E., and A. C. Spradling. "The Drosophila G-protein-coupled receptor kinase homologue Gprk2 is required for egg morphogenesis." Development 124, no. 13 (1997): 2591–602. http://dx.doi.org/10.1242/dev.124.13.2591.

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G protein signaling is a widely utilized form of extracellular communication that is mediated by a family of serpentine receptors containing seven transmembrane domains. In sensory neurons, cardiac muscle and other tissues, G protein-coupled receptors are desensitized through phosphorylation by a family of kinases, the G protein-coupled receptor kinases (GRKs). Desensitization allows a cell to decrease its response to a given signal, in the continued presence of that signal. We have identified a Drosophila mutant, gprk2(6936) that disrupts expression of a putative member of the GRK family, the
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34

Conway, Bruce R., Lisa K. Minor, Jun Z. Xu, et al. "Quantification of G-Protein Coupled Receptor Internalization Using G-Protein Coupled Receptor-Green Fluorescent Protein Conjugates with the ArrayScan™ High-Content Screening System." Journal of Biomolecular Screening 4, no. 2 (1999): 75–86. http://dx.doi.org/10.1177/108705719900400207.

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Many G-protein coupled receptors (GPCRs) undergo ligand-dependent homologous desensitization and internalization. Desensitization, defined as a decrease in the responsiveness to ligand, is accompanied by receptor aggregation on the cell surface and internalization via clathrin-coated pits to an intracellular endosomal compartment. In this study, we have taken advantage of the trafficking properties of GPCRs to develop a useful screening method for the identification of receptor mimetics. A series of studies were undertaken to evaluate the expression, functionality, and ligand-dependent traffic
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35

BÖHM, Stephan K., Eileen F. GRADY, and Nigel W. BUNNETT. "Regulatory mechanisms that modulate signalling by G-protein-coupled receptors." Biochemical Journal 322, no. 1 (1997): 1–18. http://dx.doi.org/10.1042/bj3220001.

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The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of
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36

Yadav, Dinesh Kumar, and Narendra Tuteja. "Rice G-protein coupled receptor (GPCR)." Plant Signaling & Behavior 6, no. 8 (2011): 1079–86. http://dx.doi.org/10.4161/psb.6.8.15771.

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37

Park, Paul S.-H., and Krzysztof Palczewski. "Imaging G protein–coupled receptor islands." Nature Chemical Biology 1, no. 4 (2005): 184–85. http://dx.doi.org/10.1038/nchembio0905-184.

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38

Belmonte, Stephen L., and Burns C. Blaxall. "G Protein–Coupled Receptor Kinase 5." Circulation Research 111, no. 8 (2012): 957–58. http://dx.doi.org/10.1161/circresaha.112.278432.

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39

Woodall, Meryl C., Michele Ciccarelli, Benjamin P. Woodall, and Walter J. Koch. "G Protein–Coupled Receptor Kinase 2." Circulation Research 114, no. 10 (2014): 1661–70. http://dx.doi.org/10.1161/circresaha.114.300513.

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40

Vilardaga, J. P., L. F. Agnati, K. Fuxe, and F. Ciruela. "G-protein-coupled receptor heteromer dynamics." Journal of Cell Science 123, no. 24 (2010): 4215–20. http://dx.doi.org/10.1242/jcs.063354.

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41

Wisler, James W., Howard A. Rockman, and Robert J. Lefkowitz. "Biased G Protein–Coupled Receptor Signaling." Circulation 137, no. 22 (2018): 2315–17. http://dx.doi.org/10.1161/circulationaha.117.028194.

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42

Smrcka, Alan V. "Fingerprinting G protein–coupled receptor signaling." Science Signaling 8, no. 405 (2015): fs20. http://dx.doi.org/10.1126/scisignal.aad8140.

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43

Yang, Jian, Van Anthony M. Villar, John E. Jones, Pedro A. Jose, and Chunyu Zeng. "G Protein-Coupled Receptor Kinase 4." Hypertension 65, no. 6 (2015): 1148–55. http://dx.doi.org/10.1161/hypertensionaha.115.05189.

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44

Sallese, Michele, Stefania Mariggiò, Giulia Collodel, et al. "G Protein-coupled Receptor Kinase GRK4." Journal of Biological Chemistry 272, no. 15 (1997): 10188–95. http://dx.doi.org/10.1074/jbc.272.15.10188.

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45

Ambrosio, Manuela, Alexander Zürn, and Martin J. Lohse. "Sensing G protein-coupled receptor activation." Neuropharmacology 60, no. 1 (2011): 45–51. http://dx.doi.org/10.1016/j.neuropharm.2010.08.006.

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46

Wilson, Carol J., and Meredithe L. Applebury. "Arresting G-protein coupled receptor activity." Current Biology 3, no. 10 (1993): 683–86. http://dx.doi.org/10.1016/0960-9822(93)90068-y.

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47

Rana, Brinda K., and Paul A. Insel. "Useful G-protein-coupled receptor websites." Trends in Pharmacological Sciences 22, no. 9 (2001): 485–86. http://dx.doi.org/10.1016/s0165-6147(00)01806-x.

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48

Hodavance, Sima Y., Clarice Gareri, Rachel D. Torok, and Howard A. Rockman. "G Protein–coupled Receptor Biased Agonism." Journal of Cardiovascular Pharmacology 67, no. 3 (2016): 193–202. http://dx.doi.org/10.1097/fjc.0000000000000356.

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49

Zeng, Chunyu, Van Anthony M. Villar, Gilbert M. Eisner, Scott M. Williams, Robin A. Felder, and Pedro A. Jose. "G Protein–Coupled Receptor Kinase 4." Hypertension 51, no. 6 (2008): 1449–55. http://dx.doi.org/10.1161/hypertensionaha.107.096487.

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50

Audet, Martin, and Michel Bouvier. "Restructuring G-Protein- Coupled Receptor Activation." Cell 151, no. 1 (2012): 14–23. http://dx.doi.org/10.1016/j.cell.2012.09.003.

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