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https://www.readbyqxmd.com/read/27832841/new-concepts-in-dopamine-d2-receptor-biased-signaling-and-implications-for-schizophrenia-therapy
#1
REVIEW
Nikhil M Urs, Sean M Peterson, Marc G Caron
The dopamine D2 receptor (D2R) is a G protein-coupled receptor that is a common target for antipsychotic drugs. Antagonism of D2R signaling in the striatum is thought to be the primary mode of action of antipsychotic drugs in alleviating psychotic symptoms. However, antipsychotic drugs are not clinically effective at reversing cortical-related symptoms, such as cognitive deficits in schizophrenia. While the exact mechanistic underpinnings of these cognitive deficits are largely unknown, deficits in cortical dopamine function likely play a contributing role...
October 19, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27378762/chapter-nine-cellular-roles-of-beta-arrestins-as-substrates-and-adaptors-of-ubiquitination-and-deubiquitination
#2
P-Y Jean-Charles, N J Freedman, S K Shenoy
β-Arrestin1 and β-arrestin2 are homologous adaptor proteins that are ubiquitously expressed in mammalian cells. They belong to a four-member family of arrestins that regulate the vast family of seven-transmembrane receptors that couple to heterotrimeric G proteins (7TMRs or GPCRs), and that modulate 7TMR signal transduction. β-Arrestins were originally identified in the context of signal inhibition via the 7TMRs because they competed with and thereby blocked G protein coupling to 7TMRs. Currently, in addition to their role as desensitizers of signaling, β-arrestins are appreciated as multifunctional adaptors that mediate trafficking and signal transduction of not only 7TMRs, but a growing list of additional receptors, ion channels, and nonreceptor proteins...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/26954469/deletion-of-%C3%AE-arrestin2-in-mice-limited-pancreatic-beta-cell-expansion-under-metabolic-stress-through-activation-of-jnk-pathway
#3
Ziwei Lin, Yu Zhao, Lige Song, Kaida Mu, Mingliang Zhang, Hongxia Liu, Xiaowen Li, Jian Zhao, Chen Wang, Weiping Jia
β-Arrestin2 (βarr2) is an adaptor protein that interacts with numerous signalling molecules and regulates insulin sensitivity. We reported previously that βarr2 was abundantly expressed in mouse pancreatic beta-cells, and loss of βarr2 leads to impairment of acute- and late-phase insulin secretion. In the present study, we examined the dynamic changes of beta-cell mass in βarr2-deficient (βarr2(-/-)) mice in vivo and explore the underlying mechanisms involved. βarr2(-/-) mice with luciferase exclusively overexpression in beta-cells were generated and fed with a high-fat diet (HFD)...
February 29, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/26839314/ubiquitin-specific-protease-20-regulates-the-reciprocal-functions-of-%C3%AE-arrestin2-in-toll-like-receptor-4-promoted-nuclear-factor-%C3%AE%C2%BAb-nf%C3%AE%C2%BAb-activation
#4
Pierre-Yves Jean-Charles, Lisheng Zhang, Jiao-Hui Wu, Sang-Oh Han, Leigh Brian, Neil J Freedman, Sudha K Shenoy
Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin-specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein β-arrestin2. Although β-arrestin2 effects on TRAF6 suggest an anti-inflammatory role, physiologic β-arrestin2 promotes inflammation in atherosclerosis and neointimal hyperplasia...
April 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26827791/assessment-of-response-to-beta-blockers-by-expression-of-%C3%AE-arr2-and-rhoa-rock2-in-antrum-mucosa-in-cirrhotic-patients
#5
Jonel Trebicka, Matthias von Heydebrand, Jennifer Lehmann, Flemming Tofteng, Troels Busk, Helle Lone Jensen, Johan Rohde, Thomas Reiberger, Christian Mortensen, Robert Schierwagen, Sabine Klein, Søren Møller, Flemming Bendtsen, Aleksander Krag
BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS: Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge...
June 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/26507558/%C3%AE-arrestin-2-dependence-of-%C3%AE-opioid-receptor-agonists-is-correlated-with-alcohol-intake
#6
T Chiang, K Sansuk, R M van Rijn
BACKGROUND AND PURPOSE: δ Opioid receptor agonists are being developed as potential treatments for depression and alcohol use disorders. This is particularly interesting as depression is frequently co-morbid with alcohol use disorders. Yet we have previously shown that δ receptor agonists range widely in their ability to modulate alcohol intake; certain δ receptor agonists actually increase alcohol consumption in mice. We propose that variations in β-arrestin 2 recruitment contribute to the differential behavioural profile of δ receptor agonists...
January 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26459714/selective-disruption-of-dopamine-d2-receptors-beta-arrestin2-signaling-by-mood-stabilizers
#7
Thomas Del' Guidice, Jean-Martin Beaulieu
Mood stabilizers are a heterogeneous class of drugs having antidepressant and anti-manic effects in bipolar disorders, depression and schizophrenia. Despite wide clinical applications, the mechanisms underlying their shared actions and therapeutic specificity are unknown. Here, we examine the effects of the structurally unrelated mood stabilizers lamotrigine, lithium and valproate on G protein and beta-arrestin-dependent components of dopamine D2 receptor signaling and assess their contribution to the behavioral effects of these drugs...
June 2015: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/25923671/potent-anti-hiv-chemokine-analogs-direct-post-endocytic-sorting-of-ccr5
#8
Claudia Bönsch, Mihaela Munteanu, Irène Rossitto-Borlat, Alexandre Fürstenberg, Oliver Hartley
G protein-coupled receptors (GPCRs) are desensitized and internalized following activation. They are then subjected to post-endocytic sorting (degradation, slow recycling or fast recycling). The majority of research on post-endocytic sorting has focused on the role of sequence-encoded address structures on receptors. This study focuses on trafficking of CCR5, a GPCR chemokine receptor and the principal entry coreceptor for HIV. Using Chinese Hamster Ovary cells stably expressing CCR5 we show that two different anti-HIV chemokine analogs, PSC-RANTES and 5P14-RANTES, direct receptor trafficking into two distinct subcellular compartments: the trans-Golgi network and the endosome recycling compartment, respectively...
2015: PloS One
https://www.readbyqxmd.com/read/25831532/%C3%AE-arrestin-biased-signaling-mediates-memory-reconsolidation
#9
Xing Liu, Li Ma, Hao Hong Li, Bing Huang, You Xing Li, Ye Zheng Tao, Lan Ma
A long-standing hypothesis posits that a G protein-coupled signaling pathway mediates β-adrenergic nervous system functions, including learning and memory. Here we report that memory retrieval (reactivation) induces the activation of β1-adrenergic β-arrestin signaling in the brain, which stimulates ERK signaling and protein synthesis, leading to postreactivation memory restabilization. β-Arrestin2-deficient mice exhibit impaired memory reconsolidation in object recognition, Morris water maze, and cocaine-conditioned place preference paradigms...
April 7, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25779032/the-effects-of-beta-arrestin1-deletion-on-acute-cannabinoid-activity-brain-cannabinoid-receptors-and-tolerance-to-cannabinoids-in-mice
#10
Chris S Breivogel, Manan S Vaghela
CONTEXT: Previous studies have indicated a role for beta-arrestin2 in the regulation of brain cannabinoid effects and cannabinoid CB1 receptors, but whether beta-arrestin1 has a role has not been investigated. OBJECTIVE: To determine the role of beta-arrestin1 in cannabinoid activity. MATERIALS AND METHODS: Beta-arrestin1 -/- mice and their wild-type (+/+) counterparts were assayed for antinociceptive and temperature-decreasing effects of two ligands, Δ(9)-tetrahydrocannabinol (THC) and CP55940, after both single and repeated administration...
February 2015: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/25759509/a-fluorescent-live-imaging-screening-assay-based-on-translocation-criteria-identifies-novel-cytoplasmic-proteins-implicated-in-g-protein-coupled-receptor-signaling-pathways
#11
Sandra Lecat, Hans W D Matthes, Rainer Pepperkok, Jeremy C Simpson, Jean-Luc Galzi
Several cytoplasmic proteins that are involved in G protein-coupled receptor signaling cascades are known to translocate to the plasma membrane upon receptor activation, such as beta-arrestin2. Based on this example and in order to identify new cytoplasmic proteins implicated in the ON-and-OFF cycle of G protein-coupled receptor, a live-imaging screen of fluorescently labeled cytoplasmic proteins was performed using translocation criteria. The screening of 193 fluorescently tagged human proteins identified eight proteins that responded to activation of the tachykinin NK2 receptor by a change in their intracellular localization...
May 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/25134539/indacaterol-inhibits-tumor-cell-invasiveness-and-mmp-9-expression-by-suppressing-ikk-nf-%C3%AE%C2%BAb-activation
#12
Su Ui Lee, Kyung-Seop Ahn, Min Hee Sung, Ji-Won Park, Hyung Won Ryu, Hyun-Jun Lee, Sung-Tae Hong, Sei-Ryang Oh
The β2 adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled β2-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear...
August 2014: Molecules and Cells
https://www.readbyqxmd.com/read/24905583/%C3%AE-2-adrenoceptor-involved-in-smoking-induced-airway-mucus-hypersecretion-through-%C3%AE-arrestin-dependent-signaling
#13
Yujiao Zhou, Yuan Zhang, Yang Guo, Youyi Zhang, Ming Xu, Bei He
Progression of chronic obstructive pulmonary disease is associated with small airway obstruction by accumulation of inflammatory mucous exudates. However, the mechanism of mucin hypersecretion after exposure to cigarette smoke (CS) is still not clear. In this study, we explored the contribution of β2-adrenoceptor (β2-AR) signaling to CS extract (CSE)-induced mucus hypersecretion in vitro and examined the effect of a β-blocker on airway mucin hypersecretion in vivo. NCI-H292 epithelial cell line was used to determine the contribution of β2-AR signaling to CSE-induced MUC5AC production by treatment with β2-AR antagonists propranolol and ICI118551 and β2-AR-targeted small interfering RNA...
2014: PloS One
https://www.readbyqxmd.com/read/24812278/tubulin-polymerization-disrupts-cardiac-%C3%AE-adrenergic-regulation-of-late-ina
#14
Nataliya Dybkova, Stefan Wagner, Johannes Backs, Thomas J Hund, Peter J Mohler, Thomas Sowa, Viacheslav O Nikolaev, Lars S Maier
AIMS: The anticancer drug paclitaxel (TXL) that polymerizes microtubules is associated with arrhythmias and sinus node dysfunction. TXL can alter membrane expression of Na channels (NaV1.5) and Na current (INa), but the mechanisms are unknown. Calcium/calmodulin-dependent protein kinase II (CaMKII) can be activated by β-adrenergic stimulation and regulates INa gating. We tested whether TXL interferes with isoproterenol (ISO)-induced activation of CaMKII and consequent INa regulation...
July 1, 2014: Cardiovascular Research
https://www.readbyqxmd.com/read/24317793/%C3%AE-arrestin2-plays-a-key-role-in-the-modulation-of-the-pancreatic-beta-cell-mass-in-mice
#15
Magalie A Ravier, Michele Leduc, Joy Richard, Nathalie Linck, Annie Varrault, Nelly Pirot, Morgane M Roussel, Joël Bockaert, Stéphane Dalle, Gyslaine Bertrand
AIMS/HYPOTHESIS: Beta cell failure due to progressive secretory dysfunction and limited expansion of beta cell mass is a key feature of type 2 diabetes. Beta cell function and mass are controlled by glucose and hormones/neurotransmitters that activate G protein-coupled receptors or receptor tyrosine kinases. We have investigated the role of β-arrestin (ARRB)2, a scaffold protein known to modulate such receptor signalling, in the modulation of beta cell function and mass, with a specific interest in glucagon-like peptide-1 (GLP-1), muscarinic and insulin receptors...
March 2014: Diabetologia
https://www.readbyqxmd.com/read/24162663/%C3%AE-arrestin-protects-neurons-by-mediating-endogenous-opioid-arrest-of-inflammatory-microglia
#16
X Feng, C-Y Wu, F H Burton, H H Loh, L-N Wei
Microglial activation worsens neuronal loss and contributes to progressive neurological diseases like Parkinson's disease (PD). This inflammatory progression is countered by dynorphin (Dyn), the endogenous ligand of the kappa-opioid receptor (KOR). We show that microglial β-arrestin mediates the ability of Dyn/KOR to limit endotoxin-elicited production of pro-inflammatory effectors and cytokines, subsequently protecting neurons from inflammation-induced neurotoxicity. Agonist-activated KOR enhances the interaction of β-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1), disrupting TAK1-TAB1 mediated pro-inflammatory gene expression...
March 2014: Cell Death and Differentiation
https://www.readbyqxmd.com/read/24140428/different-amounts-of-ejaculatory-activity-a-natural-rewarding-behavior-induce-differential-mu-and-delta-opioid-receptor-internalization-in-the-rat-s-ventral-tegmental-area
#17
René Garduño-Gutiérrez, Martha León-Olea, Gabriela Rodríguez-Manzo
Opioid receptors internalize upon specific agonist stimulation. The in vivo significance of receptor internalization is not well established, partly due to the limited in vivo models used to study this phenomenon. Ejaculation promotes endogenous opioid release which activates opioid receptors at the brain, including the mesolimbic system and medial preoptic area. The objective of the present work was to analyze if there was a correlation between the degree of in vivo mu (MOR) and delta opioid receptor (DOR) internalization in the ventral tegmental area and the execution of different amounts of ejaculatory behavior of male rats...
December 6, 2013: Brain Research
https://www.readbyqxmd.com/read/24094141/the-influence-of-beta-arrestin2-on-cannabinoid-cb1-receptor-coupling-to-g-proteins-and-subcellular-localization-and-relative-levels-of-beta-arrestin1-and-2-in-mouse-brain
#18
Christopher S Breivogel, Vanita Puri, Jonathan M Lambert, Deryck K Hill, John W Huffman, Raj K Razdan
CONTEXT: Beta-arrestins are known to couple to some G-protein-coupled receptors (GPCRs) to regulate receptor internalization, G-protein coupling and signal transduction, but have not been investigated for most receptors, and for very few receptors in vivo. Previous studies have shown that beta-arrestin2 deletion enhances the efficacy of specific cannabinoid agonists. OBJECTIVE: The present study hypothesized that brain cannabinoid CB1 receptors are regulated by beta-arrestin2...
December 2013: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/24069330/gpr3-stimulates-a%C3%AE-production-via-interactions-with-app-and-%C3%AE-arrestin2
#19
Christopher D Nelson, Morgan Sheng
The orphan G protein-coupled receptor (GPCR) GPR3 enhances the processing of Amyloid Precursor Protein (APP) to the neurotoxic beta-amyloid (Aβ) peptide via incompletely understood mechanisms. Through overexpression and shRNA knockdown experiments in HEK293 cells, we show that β-arrestin2 (βarr2), a GPCR-interacting scaffold protein reported to bind γ-secretase, is an essential factor for GPR3-stimulated Aβ production. For a panel of GPR3 receptor mutants, the degree of stimulation of Aβ production correlates with receptor-β-arrestin binding and receptor trafficking to endocytic vesicles...
2013: PloS One
https://www.readbyqxmd.com/read/23865508/triphenylmethane-dye-activation-of-beta-arrestin
#20
Larry S Barak, Yushi Bai, Joshua C Snyder, Jiangbo Wang, Wei Chen, Marc G Caron
β-Arrestins regulate G protein-coupled receptor signaling as competitive inhibitors and protein adaptors. Low molecular weight biased ligands that bind receptors and discriminate between the G protein dependent arm and β-arrestin, clathrin-associated arm of receptor signaling are considered therapeutically valuable as a result of this distinctive pharmacological behavior. Other than receptor agonists, compounds that activate β-arrestins are not available. We show that within minutes of exposure to the cationic triphenylmethane dyes malachite green and brilliant green, tissue culture cells recruit β-arrestins to clathrin scaffolds in a receptor-activation independent manner...
August 13, 2013: Biochemistry
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