All Outputs (55)

Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1 (2019)
Journal Article
Sanchez, J., Lane, R., Canals, M., & Stone, M. J. (2019). Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1. International Journal of Molecular Sciences, 20(10), 1-15. https://doi.org/10.3390/ijms20102417

Leukocyte migration, a hallmark of the inflammatory response, is stimulated by the interactions between chemokines, which are expressed in injured or infected tissues, and chemokine receptors, which are G protein-coupled receptors (GPCRs) expressed i... Read More about Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1.

GRK mediates μ-opioid receptor plasma membrane reorganization (2019)
Journal Article
Gondin, A. B., Halls, M. L., Canals, M., & Briddon, S. J. (2019). GRK mediates μ-opioid receptor plasma membrane reorganization. Frontiers in Molecular Neuroscience, 12, https://doi.org/10.3389/fnmol.2019.00104

Differential regulation of the μ-opioid receptor (MOP) has been linked to the development of opioid tolerance and dependence which both limit the clinical use of opioid analgesics. At a cellular level, MOP regulation occurs via receptor phosphorylati... Read More about GRK mediates μ-opioid receptor plasma membrane reorganization.

G protein-coupled receptors are dynamic regulators of digestion and targets for digestive diseases (2019)
Journal Article
Canals, M., Poole, D. P., Veldhuis, N. A., Schmidt, B. L., & Bunnett, N. W. (2019). G protein-coupled receptors are dynamic regulators of digestion and targets for digestive diseases. Gastroenterology, 156(6), 1600-1616. https://doi.org/10.1053/j.gastro.2019.01.266

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins. Within the gastrointestinal tract, GPCRs expressed by epithelial cells sense contents of the lumen, and GPCRs expressed by epithelial cells, myocytes, neu... Read More about G protein-coupled receptors are dynamic regulators of digestion and targets for digestive diseases.

Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer (2019)
Journal Article
Blasco-Benito, S., Moreno, E., Seijo-Vila, M., Tundidor, I., Andradas, C., Caffarel, M. M., …Sánchez, C. (2019). Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer. Proceedings of the National Academy of Sciences, 116(9), 3863-3872. https://doi.org/10.1073/pnas.1815034116

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New therapeut... Read More about Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer.

Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1 (2018)
Journal Article
Sanchez, J., e Huma, Z., Lane, J., Liu, X., Bridgford, J. L., Payne, R. J., …Stone, M. J. (2018). Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1. Journal of Biological Chemistry, 294(10), 3464-3475. https://doi.org/10.1074/jbc.ra118.006535

© 2019 Sanchez et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Interactions between secreted immune proteins called chemokines and their cognate G protein– coupled receptors regulate the t... Read More about Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1.

Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations (2018)
Journal Article
Civciristov, S., Ellisdon, A. M., Suderman, R., Pon, C. K., Evans, B. A., Kleifeld, O., …Halls, M. L. (2018). Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations. Science Signaling, 11(551), Article eaan1188. https://doi.org/10.1126/scisignal.aan1188

G protein–coupled receptors (GPCRs) are the largest class of cell surface signaling proteins, participate in nearly all physiological processes, and are the targets of 30% of marketed drugs. Typically, nanomolar to micromolar concentrations of ligand... Read More about Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations.

Hormones, neurotransmitters, growth factors, receptors, and signaling: Inflammation-associated changes in DOR expression and function in the mouse colon (2018)
Journal Article
Dicello, J., Saito, A., Rajasekhar, P., Eriksson, E., McQuade, R., Nowell, C., …Poole, D. (2018). Hormones, neurotransmitters, growth factors, receptors, and signaling: Inflammation-associated changes in DOR expression and function in the mouse colon. American Journal of Physiology, 315(4), G544-G559. https://doi.org/10.1152/ajpgi.00025.2018

Endoge-nous opioids activate opioid receptors (ORs) in the enteric nervous system to control intestinal motility and secretion. The μ-OR mediates the deleterious side effects of opioid analgesics, including constipation, respiratory depression, and a... Read More about Hormones, neurotransmitters, growth factors, receptors, and signaling: Inflammation-associated changes in DOR expression and function in the mouse colon.

Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid -opioid receptor desensitization (2018)
Journal Article
Miess, E., Gondin, A. B., Yousuf, A., Steinborn, R., Mösslein, N., Yang, Y., …Canals, M. (2018). Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid -opioid receptor desensitization. Science Signaling, 11(539), Article eaas9609. https://doi.org/10.1126/scisignal.aas9609

Copyright © 2018 The Authors. G protein receptor kinases (GRKs) and -arrestins are key regulators of -opioid receptor (MOR) signaling and trafficking. We have previously shown that high-efficacy opioids such as DAMGO stimulate a GRK2/3-mediated multi... Read More about Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid -opioid receptor desensitization.

Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome (2018)
Journal Article
Jimenez-Vargas, N. N., Pattison, L. A., Zhao, P., Lieu, T. M., Latorre, R., Jensen, D. D., …Bunnett, N. W. (2018). Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome. Proceedings of the National Academy of Sciences, 115(31), E7438-E7447. https://doi.org/10.1073/pnas.1721891115

© 2018 National Academy of Sciences. All rights reserved. Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contr... Read More about Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.

Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization (2018)
Journal Article
Huang, C., Lewis, C., Borg, N. A., Canals, M., Diep, H., Drummond, G. R., …Stone, M. J. (2018). Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization. Journal of Proteome Research, 17(4), 1485-1499. https://doi.org/10.1021/acs.jproteome.7b00828

Macrophages, which accumulate in tissues during inflammation, may be polarized toward pro-inflammatory (M1) or tissue reparative (M2) phenotypes. The balance between these phenotypes can have a substantial influence on the outcome of inflammatory dis... Read More about Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization.

Pharmacologic evidence for a putative conserved allosteric site on opioid receptors (2018)
Journal Article
Livingston, K., Stanczyk, M., Burford, N., Alt, A., Canals, M., & Traynor, J. (2018). Pharmacologic evidence for a putative conserved allosteric site on opioid receptors. Molecular Pharmacology, 93(2), 157-167. https://doi.org/10.1124/mol.117.109561

Allosteric modulators of G protein-coupled receptors, including opioid receptors, have been proposed as possible therapeutic agents with enhanced selectivity. BMS-986122 is a positive allosteric modulator (PAM) of the μ-opioid receptor (μ-OR). BMS-98... Read More about Pharmacologic evidence for a putative conserved allosteric site on opioid receptors.

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies (2018)
Journal Article
Lam, R., Gondin, A. B., Canals, M., Kellam, B., Briddon, S. J., Graham, B., & Scammells, P. J. (2018). Fluorescently Labeled Morphine Derivatives for Bioimaging Studies. Journal of Medicinal Chemistry, 61(3), 1316-1329. https://doi.org/10.1021/acs.jmedchem.7b01811

Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose; patients often become tolerant and dependent on these drugs, which remains a major health... Read More about Fluorescently Labeled Morphine Derivatives for Bioimaging Studies.

Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission (2017)
Journal Article
Yarwood, R., Imlach, W., Lieu, T., Veldhuis, N., Jensen, D., Herenbrink, C., …Bunnett, N. (2017). Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission. Proceedings of the National Academy of Sciences, 114(46), 12309-12314. https://doi.org/10.1073/pnas.1706656114

G protein-coupled receptors (GPCRs) are considered to function primarily at the plasma membrane, where they interact with extracellular ligands and couple to G proteins that transmit intracellular signals. Consequently, therapeutic drugs are designed... Read More about Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission.

Genetically Encoded FRET Biosensors to Illuminate Compartmentalised GPCR Signalling (2017)
Journal Article
Halls, M., & Canals, M. (2018). Genetically Encoded FRET Biosensors to Illuminate Compartmentalised GPCR Signalling. Trends in Pharmacological Sciences, 39(2), 148-157. https://doi.org/10.1016/j.tips.2017.09.005

Genetically encoded Förster resonance energy transfer (FRET) biosensors have been instrumental to our understanding of how intracellular signalling is organised and regulated within cells. In the last decade, the toolbox, dynamic range and applicatio... Read More about Genetically Encoded FRET Biosensors to Illuminate Compartmentalised GPCR Signalling.

Ticks from diverse genera encode chemokine-inhibitory evasin proteins (2017)
Journal Article
Hayward, J., Sanchez, J., Perry, A., Huang, C., Rodriguez Valle, M., Canals, M., …Stone, M. J. (2017). Ticks from diverse genera encode chemokine-inhibitory evasin proteins. Journal of Biological Chemistry, 292(38), 15670-15680. https://doi.org/10.1074/jbc.M117.807255

To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules. In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named “evasins,” which bind to host c... Read More about Ticks from diverse genera encode chemokine-inhibitory evasin proteins.

Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief (2017)
Journal Article
Porter, C. J., Lieu, T. M., Jensen, D. D., Lieu, T., Halls, M. L., Veldhuis, N. A., …Bunnett, N. W. (2017). Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Science Translational Medicine, 9(392), Article eaal3447. https://doi.org/10.1126/scitranslmed.aal3447

© 2017, American Association for the Advancement of Science. Typically considered to be cell surface sensors of extracellular signals, heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) control many pathophysiological processes... Read More about Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief.

Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2 (2017)
Journal Article
Huma, Z. E., Sanchez, J., Lim, H. D., Bridgford, J. L., Huang, C., Parker, B. J., …Stone, M. J. (2017). Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2. Science Signaling, 10(480), Article eaai8529. https://doi.org/10.1126/scisignal.aai8529

Chemokines and their receptors collectively orchestrate the trafficking of leukocytes in normal immune function and inflammatory diseases. Different chemokines can induce distinct responses at the same receptor. In comparison to monocyte chemoattract... Read More about Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2.

Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig (2016)
Journal Article
Lay, J., Carbone, S. E., DiCello, J. J., Bunnett, N. W., Canals, M., & Poole, D. P. (2016). Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig. AJP - Gastrointestinal and Liver Physiology, 311(2), G252-G266. https://doi.org/10.1152/ajpgi.00184.2016

© 2016 the American Physiological Society. The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut f... Read More about Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.

Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor (2016)
Journal Article
Thompson, G., Lane, J., Coudrat, T., Sexton, P., Christopoulos, A., & Canals, M. (2016). Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor. Biochemical Pharmacology, 113, 70-87. https://doi.org/10.1016/j.bcp.2016.05.014

Biased agonism describes the ability of distinct G protein-coupled receptor (GPCR) ligands to stabilise distinct receptor conformations leading to the activation of different cell signalling pathways that can deliver different physiologic outcomes. T... Read More about Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor.

Protein kinase D and Gβγ subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane (2016)
Journal Article
Jensen, D. D., Zhao, P., Jimenez-Vargas, N. N., Lieu, T. M., Gerges, M., Yeatman, H. R., …Bunnett, N. W. (2016). Protein kinase D and Gβγ subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane. Journal of Biological Chemistry, 291(21), 11285-11299. https://doi.org/10.1074/jbc.M115.710681

Agonist-evoked endocytosis of G protein-coupled receptors has been extensively studied. The mechanisms by which agonists stimulate mobilization and plasma membrane translocation of G protein-coupled receptors from intracellular stores are unexplored.... Read More about Protein kinase D and Gβγ subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane.