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Arrestin

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https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#1
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28632878/identification-of-novel-g-protein-coupled-receptor-143-ligands-as-pharmacologic-tools-for-investigating-x-linked-ocular-albinism
#2
Elisabetta De Filippo, Prashiela Manga, Anke C Schiedel
Purpose: GPR143 regulates melanosome biogenesis and organelle size in pigment cells. The mechanisms underlying receptor function remain unclear. G protein-coupled receptors (GPCRs) are excellent pharmacologic targets; thus, we developed and applied a screening approach to identify potential GPR143 ligands and chemical modulators. Methods: GPR143 interacts with β-arrestin; we therefore established a β-arrestin recruitment assay to screen for compounds that modulate activity...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28632846/suppression-of-hsp27-restores-retinal-function-and-protects-photoreceptors-from-apoptosis-in-a-light-induced-retinal-degeneration-animal-model
#3
Chih-Cheng Chien, Chi-Jung Huang, Lu-Tai Tien, Yu-Che Cheng, Chia-Ying Ke, Yih-Jing Lee
Purpose: We used a light-induced retinal degeneration animal model to investigate possible roles of heat shock protein 27 (HSP27) in retinal/photoreceptor protection. Methods: Sprague-Dawley rats were used for the light-induced retinal degeneration animal model. The histology of eye sections was observed for morphologic changes in the retina. Cell apoptosis was examined in each group using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electroretinography was used to evaluate retinal function...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28631356/immune-tolerance-effect-in-mesenteric-lymph-node-lymphocytes-of-geniposide-on-adjuvant-arthritis-rats
#4
Zheng-Rong Zhang, Hong Wu, Rong Wang, Shu-Ping Li, Li Dai, Wen-Yu Wang
Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague-Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization...
June 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#5
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626043/the-diverse-roles-of-arrestin-scaffolds-in-g-protein-coupled-receptor-signaling
#6
REVIEW
Yuri K Peterson, Louis M Luttrell
The visual/β-arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein-coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/β-arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking...
July 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28619258/rho-kinase-dependent-desensitization-of-gpr39-a-unique-mechanism-of-gpcr-downregulation
#7
Yuji Shimizu, Ryokichi Koyama, Tomohiro Kawamoto
GPR39, a G-protein-coupled receptor activated by zinc, reportedly activates multiple intracellular signaling pathways via Gs, Gq, G12/13, and β-arrestin, but little is known about downregulation of the receptor upon its activation. To our knowledge, this is the first report on the mechanism of feedback regulation of GPR39 function determined in GPR39-expressing HEK293 cells (HEK293-GPR39) as a model cell system. In HEK293-GPR39 cells, GPR39-C3, which is a positive allosteric modulator, activated cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment...
June 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28615320/differential-phosphorylation-signals-control-endocytosis-of-gpr15
#8
Yukari Okamoto, Sojin Shikano
GPR15 is an orphan G protein-coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin-dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. Ala mutation of the distal C-terminal Arg(354) or Ser(357), which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the endocytosis while phosphomimetic mutation of Ser(357) to Asp did not...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28611418/arrestins-contribute-to-amyloid-beta-induced-cell-death-via-modulation-of-autophagy-and-the-%C3%AE-7nach-receptor-in-sh-sy5y-cells
#9
Yi-Qing Liu, Meng-Qi Jia, Zhao-Hong Xie, Xiao-Fei Liu, Hui-Yang, Xiao-Lei Zheng, Hui-Qing Yuan, Jian-Zhong Bi
Amyloid β-protein (Aβ) is believed to contribute to the development of Alzheimer's disease (AD). Here we showed that Aβ25-35 rapidly caused activation of autophagy, subsequently leading to reduction of autophagy associated with cellular apoptosis. Further investigation revealed that the accumulation of β-arrestin 1 (ARRB1) caused by Aβ25-35 contributed to the induction of autophagic flux. The depletion of ARRB1 led to decreases in the expression of LC3B, Atg7, and Beclin-1, which are essential for the initiation of autophagy...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610829/corrigendum-to-%C3%AE-arrestins-negatively-control-human-adrenomedullin-type-1-receptor-internalization-biochem-biophys-res-commun-487-2-2017-438-443
#10
Kenji Kuwasako, Kazuo Kitamura, Sayaka Nagata, Toshio Sekiguchi, Danfeng Jiang, Manabu Murakami, Yuichi Hattori, Johji Kato
No abstract text is available yet for this article.
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28600951/structural-mechanism-of-arrestin-activation
#11
REVIEW
Patrick Scheerer, Martha E Sommer
The large and multifunctional family of G protein-coupled receptors (GPCRs) are regulated by a small family of structurally conserved arrestin proteins. In order to bind an active GPCR, arrestin must first be activated by interaction with the phosphorylated receptor C-terminus. Recent years have witnessed major developments in high-resolution crystal structures of pre-active arrestins and arrestin or arrestin-derived peptides in complex with an active GPCR. Although each structure individually offers only a limited snapshot, taken together and interpreted in light of recent complementary functional data, they offer valuable insight into how arrestin is activated by and couples to a phosphorylated active GPCR...
June 7, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28594402/arrdc4-regulates-enterovirus-71-induced-innate-immune-response-by-promoting-k63-polyubiquitination-of-mda5-through-trim65
#12
Jun Meng, Zhenyu Yao, Yaqing He, Renli Zhang, Yanwei Zhang, Xiangjie Yao, Hong Yang, Long Chen, Zhen Zhang, Hailong Zhang, Xueqin Bao, Gang Hu, Tangchun Wu, Jinquan Cheng
Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28591710/selective-inhibitors-of-nuclear-export-sine-compounds-block-proliferation-and-migration-of-triple-negative-breast-cancer-cells-by-restoring-expression-of-arrdc3
#13
Young Hwa Soung, Trinayan Kashyap, Thalia Nguyen, Garima Yadav, Hua Chang, Yosef Landesman, Jun Chung
Arrestin-related domain-containing protein-3 (ARRDC3) is one of 6 mammalian arrestins, which suppresses metastasis by inducing degradation of phosphorylated β2-adrenergic receptor (β2 AR) and integrin β4 (ITG β4). Our previous studies demonstrated that expression of ARRDC3 is epigentically silenced in Triple Negative Breast Cancer (TNBC) cells, and the forced expression of ARRDC3 significantly reduced the invasive potential of TNBC cells. In the current study, we found that Selective Inhibitors of Nuclear Export (SINE) compounds (KPT-185 and selinexor (KPT-330)) restore ARRDC3 expression in TNBC cell lines (MDA-MB-231 and MDA-MB-468) at both the mRNA and protein level in a dose and time course dependent manner...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588446/purkinje-cell-degeneration-and-motor-coordination-deficits-in-a-new-mouse-model-of-autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay
#14
Man Ding, Chao Weng, Shanghua Fan, Qian Cao, Zuneng Lu
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28587876/strength-of-cholinergic-tone-dictates-the-polarity-of-dopamine-d2-receptor-modulation-of-striatal-cholinergic-interneuron-excitability-in-dyt1-dystonia
#15
Mariangela Scarduzio, Chelsea N Zimmerman, Karen L Jaunarajs, Qin Wang, David G Standaert, Lori L McMahon
Balance between cholinergic and dopaminergic signaling is central to striatal control of movement and cognition. In dystonia, a common disorder of movement, anticholinergic therapy is often beneficial. This observation suggests there is a pathological increase in cholinergic tone, yet direct confirmation is lacking. In DYT1, an early-onset genetic form of dystonia caused by a mutation in the protein torsinA (TorA), the suspected heightened cholinergic tone is commonly attributed to faulty dopamine D2 receptor (D2R) signaling where D2R agonists cause excitation of striatal cholinergic interneurons (ChIs), rather than the normal inhibition of firing observed in wild-type animals, an effect known as "paradoxical excitation"...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28586439/ramp2-influences-glucagon-receptor-pharmacology-via-trafficking-and-signaling
#16
Jaimini Cegla, Ben J Jones, James V Gardiner, David J Hodson, Thomas Marjot, Emma R McGlone, Tricia M Tan, Stephen R Bloom
Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we have investigated the interaction of the GCGR with RAMP2, a member of the family of Receptor Activity Modifying Proteins.We have used a combination of competition binding experiments, cell surface ELISA, functional assays assessing the Gαs and Gq pathways and β-arrestin recruitment, and siRNA knockdown to examine the effect of RAMP2 on the GCGR...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28585805/ligand-specific-restriction-of-extracellular-conformational-dynamics-constrains-signaling-of-the-m2-muscarinic-receptor
#17
Marcel Bermudez, Andreas Bock, Fabian Krebs, Ulrike Holzgrabe, Klaus Mohr, Martin J Lohse, Gerhard Wolber
G protein-coupled receptors transmit extracellular signals across cell membranes via different G protein classes and β-arrestins. Some pathways may be therapeutically beneficial, whereas others may be detrimental under certain pathophysiological conditions. For many GPCRs, biased agonists are available, which preferentially signal through one pathway or a subset of pathways, and harnessing biased agonism could be a potential novel therapeutic strategy. However, the incomplete mechanistic understanding of biased agonism hampers rational design of biased ligands...
June 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28584054/conformational-biosensors-reveal-allosteric-interactions-between-heterodimeric-at1-angiotensin-and-prostaglandin-f2%C3%AE-receptors
#18
Rory Sleno, Dominic Devost, Darlaine Pétrin, Alice Zhang, Kyla Bourque, Yuji Shinjo, Junken Aoki, Asuka Inoue, Terence E Hébert
G protein-coupled receptors (GPCRs) are conformationally dynamic proteins transmitting ligand-encoded signals in multiple ways. This transmission is highly complex and achieved through induction of distinct GPCR conformations, which preferentially drive specific receptor-mediated signaling events. This conformational capacity can be further enlarged via allosteric effects between dimers, warranting further study of these effects. Using GPCR conformation-sensitive biosensors, we investigated allosterically induced conformational changes in the recently reported F prostanoid (FP)/angiotensin II type 1 receptor (AT1R) heterodimer...
June 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28583844/nociceptin-orphanin-fq-antagonizes-lipopolysaccharide-stimulated-proliferation-migration-and-inflammatory-signaling-in-human-glioblastoma-u87-cells
#19
Andrea Bedini, Monica Baiula, Gabriele Vincelli, Francesco Formaggio, Sara Lombardi, Marco Caprini, Santi Spampinato
Glioblastoma is among the most aggressive brain tumors and has an exceedingly poor prognosis. Recently, the importance of the tumor microenvironment in glioblastoma cell growth and progression has been emphasized. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and endogenous ligands originating from dying cells or the extracellular matrix involved in host defense and in inflammation. G-protein coupled receptors (GPCRs) have gained interest in anti-tumor drug discovery due to the role that they directly or indirectly play by transactivating other receptors, causing cell migration and proliferation...
June 2, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28581517/functional-antagonism-of-%C3%AE-arrestin-isoforms-balance-igf-1r-expression-and-signalling-with-distinct-cancer-related-biological-outcomes
#20
N Suleymanova, C Crudden, T Shibano, C Worrall, I Oprea, A Tica, G A Calin, A Girnita, L Girnita
With very similar 3D structures, the widely expressed β-arrestin isoforms 1 and 2 play at times identical, distinct or even opposing roles in regulating various aspects of G protein-coupled receptors (GPCR) expression and signalling. Recent evidence recognizes the β-arrestin system as a key regulator of not only GPCRs, but also receptor tyrosine kinases, including the highly cancer relevant insulin-like growth factor type 1 receptor (IGF-1R). Binding of β-arrestin1 to IGF-1R leads to ligand-dependent degradation of the receptor and generates additional MAPK/ERK signalling, protecting cancer cells against anti-IGF-1R therapy...
June 5, 2017: Oncogene
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