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https://www.readbyqxmd.com/read/28719611/rna-sequencing-to-determine-the-contribution-of-kinase-receptor-transactivation-to-g-protein-coupled-receptor-signalling-in-vascular-smooth-muscle-cells
#1
Danielle Kamato, Venkata Vijayanand Bhaskarala, Nitin Mantri, Tae Gyu Oh, Dora Ling, Reearna Janke, Wenhua Zheng, Peter J Little, Narin Osman
G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR)...
2017: PloS One
https://www.readbyqxmd.com/read/28718821/tick-haller-s-organ-a-new-paradigm-for-arthropod-olfaction-how-ticks-differ-from-insects
#2
Ann L Carr, Robert D Mitchell Iii, Anirudh Dhammi, Brooke W Bissinger, Daniel E Sonenshine, R Michael Roe
Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller's organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller's organ), we characterized 1st leg specific and putative Haller's organ specific transcripts from adult American dog ticks, Dermacentor variabilis...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28700749/correction-adipocyte-arrestin-domain-containing-3-protein-arrdc3-regulates-uncoupling-protein-1-ucp1-expression-in-white-adipose-independently-of-canonical-changes-in-%C3%AE-adrenergic-receptor-signaling
#3
Shannon H Carroll, Ellen Zhang, Bing F Wang, Katherine B LeClair, Arifeen Rahman, David E Cohen, Jorge Plutzky, Parth Patwari, Richard T Lee
[This corrects the article DOI: 10.1371/journal.pone.0173823.].
2017: PloS One
https://www.readbyqxmd.com/read/28687596/expression-and-light-dependent-translocation-of-%C3%AE-arrestin-in-the-visual-system-of-the-terrestrial-slug-limax-valentianus
#4
Ryota Matsuo, Yuka Takatori, Shun Hamada, Mitsumasa Koyanagi, Yuko Matsuo
Vertebrates, cephalopods, and arthropods are equipped with eyes having the highest spatiotemporal resolution among the animal phyla. In parallel, it is only the animals in these three phyla that have visual arrestin specialized for the termination of visual signaling triggered by opsin, in addition to ubiquitously expressed β-arrestin that serves in terminating general G protein-coupled receptor signaling. Indeed, visual arrestin in Drosophila and rodents translocates to the opsin-rich subcellular region in response to light to reduce the overall sensitivity of photoreceptors in an illuminated environment (i...
July 7, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28683816/uncovering-missing-pieces-duplication-and-deletion-history-of-arrestins-in-deuterostomes
#5
Henrike Indrischek, Sonja J Prohaska, Vsevolod V Gurevich, Eugenia V Gurevich, Peter F Stadler
BACKGROUND: The cytosolic arrestin proteins mediate desensitization of activated G protein-coupled receptors (GPCRs) via competition with G proteins for the active phosphorylated receptors. Arrestins in active, including receptor-bound, conformation are also transducers of signaling. Therefore, this protein family is an attractive therapeutic target. The signaling outcome is believed to be a result of structural and sequence-dependent interactions of arrestins with GPCRs and other protein partners...
July 6, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28679059/role-and-potential-targeting-of-hepatic-apurinic-apyrimidinic-endonuclease-1-and-cyclin-dependent-kinase-4-in-hepatocellular-carcinoma
#6
Kadry Sadek, Tarek Abouzed, Sherif Nasr, Moustafa Shukry
Apurinic/apyrimidinic endonuclease/redox element 1 (APE1/Ref-1) is a pervasive multifunctional protein required in the DNA base extraction repair (BER) pathway and a noteworthy reducing-oxidizing (redox) factor that upgrades the authoritative of various transcription components to DNA. Cyclin-dependent kinases (CDKs) assume a key part in directing the movement of the cell-cycle. The present study evaluates the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in rats...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28657744/discovery-of-n-substituted-2-phenylcyclopropylmethylamines-as-functionally-selective-serotonin-2c-5-ht2c-receptor-agonists-for-potential-use-as-antipsychotic-medications
#7
Guiping Zhang, Jianjun Cheng, John D McCorvy, Paul J Lorello, Barbara J Caldarone, Bryan L Roth, Alan P Kozikowski
A series of N-substituted 2-phenylcyclopropylmethylamines were designed and synthesized, with the aim of finding 5-HT2C-selective agonists with preference for Gq signaling. A number of these compounds exhibit 5-HT2C selectivity with preference for Gq-mediated signaling compared with β-arrestin recruitment. Furthermore, the N-methyl compound (+)-15a, which displayed an EC50 of 23 nM in the calcium flux assay while showing no β-arrestin recruitment activity, is the most functionally-selective 5-HT2C agonist reported to date...
June 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28652403/protease-activated-receptor-4-and-p2y12-dimerize-co-internalize-and-activate-akt-signaling-via-endosomal-recruitment-of-%C3%AE-arrestin
#8
Thomas H Smith, Julia G Li, Michael R Dores, JoAnn Trejo
Vascular inflammation and thrombosis requires the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor P2Y12 to coordinate β-arrestin-mediated Akt signaling, an important mediator of integrin activation. However, the mechanism by which the PAR4-P2Y12 dimer controls β-arrestin dependent Akt signaling is not known...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28652372/muscarinic-receptor-regulates-extracellular-signal-regulated-kinase-by-two-modes-of-arrestin-binding
#9
Seung-Ryoung Jung, Christopher Kushmerick, Jong Bae Seo, Duk-Su Koh, Bertil Hille
Binding of agonists to G-protein-coupled receptors (GPCRs) activates heterotrimeric G proteins and downstream signaling. Agonist-bound GPCRs are then phosphorylated by protein kinases and bound by arrestin to trigger desensitization and endocytosis. Arrestin plays another important signaling function. It recruits and regulates activity of an extracellular signal-regulated kinase (ERK) cascade. However, molecular details and timing of ERK activation remain fundamental unanswered questions that limit understanding of how arrestin-dependent GPCR signaling controls cell functions...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28651823/novel-structural-insights-into-gpcr-%C3%AE-arrestin-interaction-and-signaling
#10
REVIEW
Ravi Ranjan, Hemlata Dwivedi, Mithu Baidya, Mohit Kumar, Arun K Shukla
G protein-coupled receptors (GPCRs) are major signal recognition and transmission units in the plasma membrane. The interaction of activated and phosphorylated GPCRs with the multifunctional adaptor proteins β-arrestins (βarrs) is crucial for regulation of their signaling and functional outcomes. Over the past few years, a range of structural, biochemical, and cellular studies have revealed novel insights into GPCR-βarr interaction and signaling. Some of these findings have come as a surprise and therefore have the potential to significantly refine the conceptual framework of the GPCR-βarr system...
June 23, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28650340/hepatic-%C3%AE-arrestin-2-is-essential-for-maintaining-euglycemia
#11
Lu Zhu, Mario Rossi, Yinghong Cui, Regina J Lee, Wataru Sakamoto, Nicole A Perry, Nikhil M Urs, Marc G Caron, Vsevolod V Gurevich, Grzegorz Godlewski, George Kunos, Minyong Chen, Wei Chen, Jürgen Wess
An increase in hepatic glucose production (HGP) represents a key feature of type 2 diabetes. This deficiency in metabolic control of glucose production critically depends on enhanced signaling through hepatic glucagon receptors (GCGRs). Here, we have demonstrated that selective inactivation of the GPCR-associated protein β-arrestin 2 in hepatocytes of adult mice results in greatly increased hepatic GCGR signaling, leading to striking deficits in glucose homeostasis. However, hepatocyte-specific β-arrestin 2 deficiency did not affect hepatic insulin sensitivity or β-adrenergic signaling...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28649993/kappa-opioid-receptor-activation-in-dopamine-neurons-disrupts-behavioral-inhibition
#12
Antony D Abraham, Harrison M Fontaine, Allisa J Song, Mackenzie M Andrews, Madison A Baird, Brigitte L Kieffer, Benjamin B Land, Charles Chavkin
The dynorphin/kappa opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rates (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28648738/current-topics-in-angiotensin-ii-type-1-receptor-research-focus-on-inverse-agonism-receptor-dimerization-and-biased-agonism
#13
REVIEW
Takanobu Takezako, Hamiyet Unal, Sadashiva S Karnik, Koichi Node
Although the octapeptide hormone angiotensin II (Ang II) regulates cardiovascular and renal homeostasis through the Ang II type 1 receptor (AT1R), overstimulation of AT1R causes various human diseases, such as hypertension and cardiac hypertrophy. Therefore, AT1R blockers (ARBs) have been widely used as therapeutic drugs for these diseases. Recent basic research and clinical studies have resulted in the discovery of interesting phenomena associated with AT1R function. For example, ligand-independent activation of AT1R by mechanical stress and agonistic autoantibodies, as well as via receptor mutations, has been shown to decrease the inverse agonistic efficacy of ARBs, though the molecular mechanisms of such phenomena had remained elusive until recently...
June 23, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28646018/the-amyloid-precursor-protein-modulates-%C3%AE-2a-adrenergic-receptor-endocytosis-and-signaling-through-disrupting-arrestin-3-recruitment
#14
Fang Zhang, Mary Gannon, Yunjia Chen, Lufang Zhou, Kai Jiao, Qin Wang
The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28644418/new-mt%C3%A2-melatonin-receptor-selective-ligands-agonists-and-partial-agonists
#15
Jean A Boutin, Anne Bonnaud, Chantal Brasseur, Olivier Bruno, Nolwenn Lepretre, Peter Oosting, Sophie Coumailleau, Philippe Delagrange, Olivier Nosjean, Céline Legros
The search for melatonin receptor agonists and antagonists specific towards one of the receptor subtypes will extend our understanding of the role of this system in relaying circadian information to the body. A series of compounds derived from a hit compound discovered in a screening process led to powerful agonists specific for one of the isoform of the melatonin receptor namely, MT₂. The compounds are based on a poorly explored skeleton in the molecular pharmacology of melatonin. By changing the steric hindrance of one substituent (i...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28642577/effects-of-chronic-alcohol-exposure-on-ischemia-reperfusion-induced-acute-kidney-injury-in-mice-the-role-of-%C3%AE-arrestin-2-and-glycogen-synthase-kinase-3
#16
Lihua Wang, Yifei Zhu, Lili Wang, Jingjing Hou, Yongning Gao, Lei Shen, Jingyu Zhang
Little is known about the effects of chronic alcohol intake on the outcome of acute kidney injury (AKI). Hence, we examined the effects of chronic alcohol intake on the development of renal fibrosis following AKI in an animal model of bilateral renal ischemia-reperfusion (IR) injury. We first found that chronic alcohol exposure exacerbated bilateral IR-induced renal fibrosis and renal function impairment. This phenomenon was associated with increased bilateral IR-induced extracellular matrix deposition and an increased myofibroblast population as well as increased bilateral IR-induced expression of fibrosis-related genes in the kidneys...
June 23, 2017: Experimental & Molecular Medicine
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
#17
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
#18
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
#19
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
#20
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
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