Arrestin
G-Protein-Coupled Receptor Kinase 1
Transducin
A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.
Rod Cell Outer Segment
Vision, Ocular
Cattle
Photoreceptor Cells, Invertebrate
Retinal Rod Photoreceptor Cells
Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination.
G-Protein-Coupled Receptor Kinase 3
A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response.
Dark Adaptation
Phosphorylation
Protein Binding
Opsins
Mitogen-Activated Protein Kinase 10
Receptors, Adrenergic, beta-2
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
Ocular Physiological Processes
Retinal Cone Photoreceptor Cells
Photosensitive afferent neurons located primarily within the FOVEA CENTRALIS of the MACULA LUTEA. There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. Retinal cone cells operate in daylight vision (at photopic intensities) providing color recognition and central visual acuity.
Pecten
Myosin Type III
A subclass of myosins originally found in the photoreceptor of DROSOPHILA. The heavy chains can occur as two alternatively spliced isoforms of 132 and 174 KDa. The amino terminal of myosin type III is highly unusual in that it contains a protein kinase domain which may be an important component of the visual process.
Protein Transport
Rod Opsins
How does arrestin respond to the phosphorylated state of rhodopsin? (1/474)
Visual arrestin quenches light-induced signaling by binding to light-activated, phosphorylated rhodopsin (P-Rh*). Here we present structure-function data, which in conjunction with the refined crystal structure of arrestin (Hirsch, J. A., Schubert, C., Gurevich, V. V., and Sigler, P. B. (1999) Cell, in press), support a model for the conversion of a basal or "inactive" conformation of free arrestin to one that can bind to and inhibit the light activated receptor. The trigger for this transition is an interaction of the phosphorylated COOH-terminal segment of the receptor with arrestin that disrupts intramolecular interactions, including a hydrogen-bonded network of buried, charged side chains, referred to as the "polar core." This disruption permits structural adjustments that allow arrestin to bind to the receptor. Our mutational survey identifies residues in arrestin (Arg175, Asp30, Asp296, Asp303, Arg382), which when altered bypass the need for the interaction with the receptor's phosphopeptide, enabling arrestin to bind to activated, nonphosphorylated rhodopsin (Rh*). These mutational changes disrupt interactions and substructures which the crystallographic model and previous biochemical studies have shown are responsible for maintaining the inactive state. The molecular basis for these disruptions was confirmed by successfully introducing structure-based second site substitutions that restored the critical interactions. The nearly absolute conservation of the mutagenically sensitive residues throughout the arrestin family suggests that this mechanism is likely to be applicable to arrestin-mediated desensitization of most G-protein-coupled receptors. (+info)The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation. (2/474)
G protein-coupled signaling is utilized by a wide variety of eukaryotes for communicating information from the extracellular environment. Signal termination is achieved by the action of the arrestins, which bind to activated, phosphorylated G protein-coupled receptors. We describe here crystallographic studies of visual arrestin in its basal conformation. The salient features of the structure are a bipartite molecule with an unusual polar core. This core is stabilized in part by an extended carboxy-terminal tail that locks the molecule into an inactive state. In addition, arrestin is found to be a dimer of two asymmetric molecules, suggesting an intrinsic conformational plasticity. In conjunction with biochemical and mutagenesis data, we propose a molecular mechanism by which arrestin is activated for receptor binding. (+info)G-protein coupled receptor kinases as modulators of G-protein signalling. (3/474)
G-protein coupled receptors (GPCRs) comprise one of the largest classes of signalling molecules. A wide diversity of activating ligands induce the active conformation of GPCRs and lead to signalling via heterotrimeric G-proteins and downstream effectors. In addition, a complex series of reactions participate in the 'turn-off' of GPCRs in both physiological and pharmacological settings. Some key players in the inactivation or 'desensitization' of GPCRs have been identified, whereas others remain the target of ongoing studies. G-protein coupled receptor kinases (GRKs) specifically phosphorylate activated GPCRs and initiate homologous desensitization. Uncoupling proteins, such as members of the arrestin family, bind to the phosphorylated and activated GPCRs and cause desensitization by precluding further interactions of the GPCRs and G-proteins. Adaptor proteins, including arrestins, and endocytic machinery participate in the internalization of GPCRs away from their normal signalling milieu. In this review we discuss the roles of these regulatory molecules as modulators of GPCR signalling. (+info)Immediate upstream sequence of arrestin directs rod-specific expression in Xenopus. (4/474)
Arrestins are a family of proteins that modulate G protein-coupled receptor responses with distinct arrestin genes expressed in rods and cones. To understand the regulatory mechanisms controlling rod-specific expression, the abundant Xenopus rod arrestin cDNA and a partial genomic clone, containing the immediate upstream region and amino terminus of the polypeptide, have been characterized. The deduced polypeptide has approximately 69% identity to other vertebrate rod arrestins. Southern blot analysis and polymerase chain reaction of intronic sequences demonstrated multiple alleles for rod arrestin. DNase I footprinting with retinal proteins revealed four major DNA binding sites in the proximal promoter, coinciding with consensus sequences reported in mammalian promoters. Purified bovine Crx homeodomain and mouse Nrl proteins protected a number of these sites. A dual approach of transient embryo transfections and transgenesis was used to locate transcriptional control sequences essential for rod-specific expression in Xenopus. Constructs containing -1287/+113 of 5' upstream sequence with or without intron 1 directed high level expression, specifically in rods. A construct containing only -287/+113 directed expression of green fluorescent protein solely in rod cells. These results suggest that the Crx and Nrl binding sites in the proximal promoter are the primary cis-acting sequences regulating arrestin gene expression in rods. (+info)Successful cotransplantation of intact sheets of fetal retina with retinal pigment epithelium. (5/474)
PURPOSE: Many retinal diseases, such as macular degeneration, affect both retinal pigment epithelium (RPE) and photoreceptors. Therefore, retinal repair may require transplantation of both tissues together as a cograft. METHODS: As recipients of retina-RPE cografts, 7- to 10-week-old albino Royal College of Surgeons rats that lose their photoreceptors because of a pigment epithelium defect were used. Freshly harvested intact sheets of RPE with neural retina from pigmented normal rat fetuses were gel embedded for protection and transplanted into the subretinal space. RESULTS: After 6 to 7 weeks, with the support of the cografted RPE sheet, transplanted photoreceptors developed fully in organized parallel layers in the subretinal space. Immunohistochemistry for rhodopsin, rod alpha-transducin, and S-antigen and peanut agglutinin labeling for cone interphotoreceptor matrix domains suggested that the photoreceptors in the graft were capable of normal function. CONCLUSIONS: Freshly harvested intact sheets of fetal RPE and retina, transplanted together into the subretinal space, can develop a normal morphology. Such transplants have the potential to benefit retinal diseases with dysfunctional RPE and photoreceptors. (+info)Photoreceptor function of retinal transplants implicated by light-dark shift of S-antigen and rod transducin. (6/474)
The aim was to demonstrate functional properties of transplanted histologically normal photoreceptors. Subretinal intact-sheet transplants of fetal E17-E20 rat retinas to light-damaged albino rat eyes were fixed in light or dark, 2 to 42 weeks after transplantation, and stained immunohistochemically for certain phototransduction proteins. In light adapted transplants, transducin was predominantly found in inner segments of parallel-organized photoreceptors. Transducin shifted to the outer segments with dark-adaptation. S-antigen distribution was opposite to transducin. Rhodopsin distribution did not change. The shift of signal transduction proteins correlated to the light conditions indicates that normal phototransduction processes were established in photoreceptors of transplanted retinal sheets. (+info)Visual arrestin activity may be regulated by self-association. (7/474)
Visual arrestin is the protein responsible for rapid quenching of G-protein-coupled receptor signaling. Arrestin exists as a latent inhibitor which must be 'activated' upon contact with a phosphorylated receptor. X-ray crystal structures of visual arrestin exhibit a tetrameric arrangement wherein an asymmetric dimer with an extensive interface between conformationally different subunits is related to a second asymmetric dimer by a local two-fold rotation axis. To test the biological relevance of this molecular organization in solution, we carried out a sedimentation equilibrium analysis of arrestin at both crystallographic and physiological protein concentrations. While the tetrameric form can exist at the high concentrations used in crystallography experiments, we find that arrestin participates in a monomer/dimer equilibrium at concentrations more likely to be physiologically relevant. Solution interaction analysis of a proteolytically modified, constitutively active form of arrestin shows diminished dimerization. We propose that self-association of arrestin may provide a mechanism for regulation of arrestin activity by (i) ensuring an adequate supply for rapid quenching of the visual signal and (ii) limiting the availability of active monomeric species, thereby preventing inappropriate signal termination. (+info)Differential expression of nitric oxide synthase in experimental uveoretinitis. (8/474)
PURPOSE: To investigate the site and the cellular source of inducible nitric oxide synthase (iNOS) expression in human S-antigen peptide-induced experimental autoimmune uveoretinitis (EAU). METHODS: Twenty-one Lewis rats were sensitized with human S-antigen peptides. Three rats were killed each consecutive day from day 6 through day 12 after sensitization. Frozen sections of the enucleated eyes were analyzed for iNOS by the dual immunohistochemical method. Primary antibodies included rabbit anti-mouse iNOS combined with anti-human endothelium NOS, anti-rat lysosomal protein (ED1), or anti-rat major histocompatibility complex class II molecule (OX6) monoclonal antibodies. Secondary antibodies were fluorescein-conjugated anti-mouse IgG and streptavidin rhodamine-labeled anti-rabbit IgG. The adjacent sections were separately stained with ED1, iNOS, and glial fibrillary acidic protein (GFAP). The mouse macrophage cell line RAW 264.7 was exposed to either interferon (IFN)gamma/lipopolysaccharide (LPS) or S-antigen and to interphotoreceptor retinoid-binding protein (IRBP), myelin basic protein, and bovine serum albumin for 12 hours. Cells were harvested for detection of iNOS expression by northern blot analysis hybridization and detection of protein by immunohistochemistry. RESULTS: In the retina of eyes with EAU, ED1+/iNOS+ and OX6+/iNOS+ cells were first detected on day 9 after sensitization. These iNOS+ cells increased in number on subsequent days in parallel with the increasing severity of retinal damage. Most of the cells localized around the outer retina. In contrast, a large number of ED1+ and OX6+ cells that were localized in the uvea and conjunctiva were negative for iNOS. Retinal pigment epithelial cells did not stain for iNOS. Macrophages exposed to IFNgamma/LPS, S-antigen, and IRBP showed expression of iNOS mRNA and the protein. CONCLUSIONS: Macrophages are an important source of NO production in eyes with EAU. These macrophages preferentially express iNOS in the retina. Such a differential expression of iNOS by the macrophages appears to be related to retinal soluble proteins. (+info)
The Role Of Amphipathic Alpha-helix I in Arrestin Membrane Translocation | IOVS | ARVO Journals
Two Elements In The Two Domains of The Arrestin Molecule Determine Its Receptor Specificity | IOVS | ARVO Journals
A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese | Hereditary Ocular...
Retinal S-antigen Antibody [PDS1] - ImmuQuest
Regulation of Epithelial Morphogenesis by β-Arrestin Kurtz by Katarzyna Maria Piotrowska
Plus it
SMART: Pfam domain Arrestin N
β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix |...
Novel function of β-arrestin2 in the nucleus of mature spermatozoa | Journal of Cell Science
Crystal structure of cone arrestin at 2.3A: evolution of receptor specificity
MEK1 binds βarrestin1 directly, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated...
C5AR1 CHO-K1 β-Arrestin GPCR Assay Kit Kit-1132 - Creative BioMart
CCR4 CHO-K1 β-Arrestin GPCR Assay Kit Kit-1152 - Creative BioMart
Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2 | Science
Distinct phosphorylation sites in a prototypical GPCR differently orchestrate β-arrestin interaction, trafficking, and...
Differential role of beta-arrestin ubiquitination in agonist-promoted down-regulation of M1 vs M2 muscarinic acetylcholine...
β-Arrestin1-Biased β1-Adrenergic Receptor Signaling Regulates MicroRNA Processing | Circulation Research
Plus it
Abstract 17572: Regulation of Myocardial Collagen Synthesis and Degradation by Beta-Arrestin 1/2 in Maladaptive Ventricular...
Cutting Edge: Differential Regulation of Chemoattractant Receptor-Induced Degranulation and Chemokine Production by Receptor...
Cutting Edge: Differential Regulation of Chemoattractant Receptor-Induced Degranulation and Chemokine Production by Receptor...
GPCRs - B-arrestin
Illuminating an Arrestin Pathway to Blindness | Science Signaling
β-Arrestin and Mdm2, Unsuspected Partners in Signaling from the Cell Surface | Science Signaling
LinkLight™ U2-OS GPR101 / β-arrestin Cell Line | Bon Opus Biosciences
β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3 - Fingerprint
- Albert Einstein College of...
Download A Pharmacology Primer. Techniques for More Effective and by Terry Kenakin PDF - khlinikthantkrrm Book Archive
7:12 pm
Arrestin Orchestrates Crosstalk Between G Protein-Coupled Receptors to Modulate the Spatiotemporal Activation of ERK MAPK |...
INT116674 - wiki-pain
Tekmira
Primary and secondary structure of bovine retinal S antigen (48-kDa protein) | PNAS
Cellular Morphine Tolerance Produced by βArrestin-2-Dependent Impairment of μ-Opioid Receptor Resensitization | Journal of...
G Protein-Coupled Receptor Kinase 2, With β-Arrestin 2, Impairs Insulin-Induced Akt/Endothelial Nitric Oxide Synthase Signaling...
S-Antigen: Adoptive Transfer of Experimental Autoimmune Uveitis Following Immunization With a Small Synthetic Peptide | JAMA...
Genetic Similarities to Humans - mollusks
Molecular Regulation of Opioid Receptor Signaling
Beltran, Mol Vis 2005; 11:232-244. Figure 1.
Modulation of methuselah expression targeted to Drosophila insulin-producing cells extends life and enhances oxidative stress...
Plus it
Biological membranes | Essays in Biochemistry
kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila | Genetics
β‐arrestin‐1 mediates the TCR‐triggered re‐routing of distal receptors to the immunological synapse by a PKC‐mediated mechanism...
WikiGenes - ARR3 - arrestin 3, retinal (X-arrestin)
Arrestin C-terminal-like domain (IPR011022) | InterPro | EMBL-EBI
Arrestin C domain-containing protein - Anopheles farauti
The TXNIP gene and its putative association with human ageing
RAX - Retinal homeobox protein Rx - Homo sapiens (Human) - RAX gene & protein
Differential expression of alternative splice variants of β-arrestin-1 and -2 in rat central nervous system and peripheral...
Thioredoxin-Interacting Protein Mediates Sustained VEGFR2 Signaling in Endothelial Cells Required for AngiogenesisSignificance ...
The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration
Distinct CCK-2 Receptor Conformations Associated with β-Arrestin-2 Recruitment or Phospholipase-C Activation Revealed by a...
β-arrestin-biased agonism of β-adrenergic receptor regulates Dicer-mediated microRNA maturation to promote cardioprotective...
Publications - Yamina.org
How the protease thrombin talks to cells | PNAS
OPN1MW - Wikipedia
Chatsworth house winds up with 1000 guinea pigs after taking in survivors - The Daily
Arrestin
... -3. The second non-visual arrestin cloned was first termed β-arrestin-2 (retroactively changing the name of β-arrestin ... In mammals, arrestin-1 and arrestin-4 are largely confined to photoreceptors, whereas arrestin-2 and arrestin-3 are ubiquitous ... Arrestin-2 was the first non-visual arrestin cloned. It was first named β-arrestin simply because of the two GPCRs available in ... Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, after ...
Alpha Arrestin
... β-arrestins (also referred to as visual and non-visual arrestins) and Vps26-like arrestins proteins. The α-Arrestins are an ... The arrestin family of proteins is subdivided into α-arrestins (also referred to as arrestin-related trafficking adaptors (ARTs ... It is unclear if α-arrestins lack each of these structural features thought to distinguish the β-arrestins from the α-arrestins ... β-arrestins contain a polar core flanked on both sides by the arrestin N- and C-terminal fold domains. They also contain ...
Arrestin beta 2
Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene. ... Arrestin beta 2 is crucial for the development of tolerance to morphine and other opioids. Arrestin beta 2 has been shown to ... Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high ... Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein- ...
Arrestin beta 1
Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene. Members of arrestin/beta- ... "Entrez Gene: ARRB1 arrestin, beta 1". Peterson YK, Luttrell LM (July 2017). "The Diverse Roles of Arrestin Scaffolds in G ... "Substance P-induced trafficking of beta-arrestins. The role of beta-arrestins in endocytosis of the neurokinin-1 receptor". The ... Beta-arrestin has been shown to play a role as a scaffold that binds intermediates and may direct G-protein signaling by ...
SAG (gene)
S-arrestin is a protein that in humans is encoded by the SAG gene. Members of arrestin/beta-arrestin protein family are thought ... 1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2 ... S-arrestin, also known as S-antigen, is a major soluble protein in photoreceptor cells that is involved in desensitization of ... Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in ...
Raymond C. Stevens
Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser Nature 526: 561-567 T. Hua, K. Vemuri, M ... and the human Rhodopsin-Arrestin complex. 2016: The marijuana receptor-human Cannabinoid receptor type 1 (CB1) and the human C- ...
Κ-opioid receptor
Bruchas MR, Macey TA, Lowe JD, Chavkin C (June 2006). "Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin- ... β-arrestin antagonist Amentoflavone - non-selective; naturally-occurring AT-076 - non-selective, likely long acting; JDTic ... β-arrestin antagonist Zyklophin - selective peptide antagonist; dynorphin A analogue Aticaprant - selective Found in numerous ... β-arrestin antagonist Salvinorin A - naturally-occurring 2-Methoxymethyl salvinorin B - and its ethoxymethyl and ...
Denis Baylor
"Prolonged photoresponses in transgenic mouse rods lacking arrestin". Nature. 389 (6650): 505-509. Bibcode:1997Natur.389..505X. ...
Herkinorin
Unlike most μ-opioid receptor agonists, herkinorin does not promote the recruitment of β-arrestin 2 to the intracellular domain ... April 2008). "Herkinorin analogues with differential beta-arrestin-2 interactions". Journal of Medicinal Chemistry. 51 (8): ... arrestin interactions or receptor internalization". Molecular Pharmacology. 71 (2): 549-57. doi:10.1124/mol.106.028258. PMC ... and some other analogues related to herkinorin can recruit β-arrestins. Kurkinorin Salvinorin B methoxymethyl ether RB-64 ...
Retinal degeneration (rhodopsin mutation)
2006). "Stable rhodopsin/arrestin complex leads to retinal degeneration in a transgenic mouse model of autosomal dominant ... In this research null mutations in the rhodopsin kinase and arrestin genes, each of which plays a role in terminating rhodopsin ... Besides this, the stable rhodopsin and arrestin complexes are shown to mislocalize and accumulate in the inner segments of rod ... The R135 mutant rhodopsin is noted to form stable complex with arrestin and undergo endocytosis resulting in aberrant endocytic ...
5-HT7 receptor
Kim Y, Kim H, Lee J, Lee JK, Min SJ, Seong J, Rhim H, Tae J, Lee HJ, Choo H (August 2018). "Discovery of β-Arrestin Biased ... beta-arrestin recruitment, and receptor internalization. Inactivating antagonists all likely interact with the 5-HT7 receptor ... role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization". Receptors & Channels ...
Raul Gainetdinov
He is the author of fundamental scientific works in pharmacology of dopamine, β-Arrestins and NMDA receptors. He is a pioneer ... Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG (2005-07-29). "An Akt/β-Arrestin 2/PP2A Signaling ... "Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2". Science. 286 (5449): 2495-2498. doi:10.1126/science.286.5449.2495. ...
AP3B1
Kim YM, Barak LS, Caron MG, Benovic JL (May 2002). "Regulation of arrestin-3 phosphorylation by casein kinase II". The Journal ...
Martin J. Lohse
Lohse, Martin J.; Benovic, Jeffrey L.; Codina, Juan; Caron, Marc G.; Lefkowitz, Robert J. (22 June 1990). "β-Arrestin: a ... While working with Robert Lefkowitz at Duke University he discovered beta-arrestins, proteins that regulate the function of ...
G protein-coupled receptor
In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2- ... Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating ... Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β- ... Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an ...
Arun Kumar Shukla
Reiter, Eric; Ahn, Seungkirl; Shukla, Arun K.; Lefkowitz, Robert J. (11 January 2012). "Molecular Mechanism of β-Arrestin- ... India portal Biology portal Cell signaling Arrestin Membrane proteins Please see Selected bibliography section "Arun K. Shukla ... "Functional specialization of β-arrestin interactions revealed by proteomic analysis". Proceedings of the National Academy of ... "Global phosphorylation analysis of β-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR)". ...
Signal transduction
... via protein kinase phosphorylation or b-arrestin-dependent internalization. A study was conducted where a point mutation was ...
N-2′-Indolylnaltrexamine
van Koppen, C. J.; Jakobs, K. H. Arrestin-Independent Internalization of G Protein-Coupled Receptors. Molecular Pharmacology ... of β-arrestin and the activation of the p38 MAPK and other secondary signaling cascades that are dependent on β-arrestin. INTA ... to form a conformation to block the recruitment of a protein family known as the β-arrestins. These proteins are responsible ...
Thyrotropin-releasing hormone receptor
Differential regulation of beta-arrestins 1 and 2". The Journal of Biological Chemistry. 277 (52): 50422-30. doi:10.1074/jbc. ...
Visual phototransduction
It is this pathway, where Metarhodopsin II is phosphorylated and bound to arrestin and thus deactivated, which is thought to be ... Finally, arrestin, another protein, binds the phosphorylated metarhodopsin II, completely deactivating it. Thus, finally, ... Arrestin then completely deactivates the phosphorylated-metarhodopsin II, terminating the phototransduction cascade (restoring ...
Receptor-mediated endocytosis
August 2016). "GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling". Cell. 166 (4): 907-919. doi: ... "Absence of a stable secondary structure is not a limitation for photoswitchable inhibitors of β-arrestin/β-Adaptin 2 protein- ...
VPS26A
... which has been observed for arrestins. Moreover, Vps26 does not have similar sequences as arrestins for GPCR and phospholipid ... Both Vps26 and arrestins are composed of two structurally related β-sheet domains forming extensive interfaces with each other ... Vps26 is a 38-kDa subunit that has a two-lobed structure with a polar core that resembles the arrestin family of trafficking ... Shi H, Rojas R, Bonifacino JS, Hurley JH (2006). "The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C ...
Vasopressin receptor
The V2R continues to activate Gs after being internalized by β-arrestin rather than being desensitized. This internalized Gs ... "GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling". Cell. 166 (4): 907-19. doi:10.1016/j.cell. ... signaling by V2R is explained by the receptors ability to form "mega-complexes" consisting of a single V2R, β-arrestin, and ...
ARR3
Arrestin-C, also known as retinal cone arrestin-3, is a protein that in humans is encoded by the ARR3 gene. Arrestin GRCh38: ... "Entrez Gene: ARR3 arrestin 3, retinal (X-arrestin)". Craft CM, Whitmore DH, Wiechmann AF (1994). "Cone arrestin identified by ... Murakami A, Yajima T, Sakuma H, McLaren MJ, Inana G (Dec 1993). "X-arrestin: a new retinal arrestin mapping to the X chromosome ... 2002). "Mouse cone arrestin expression pattern: light induced translocation in cone photoreceptors". Mol. Vis. 8: 462-71. PMID ...
Smoothened
"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2". Science. 306 (5705): 2257-60. Bibcode: ...
Oguchi disease
These include mutations in the arrestin gene or the rhodopsin kinase gene. The condition is more frequent in individuals of ...
GRK4
Arrestin binding to a phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to a phosphorylated, active receptor ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ... the GRK/arrestin system serves as a signaling switch for G protein-coupled receptors. GRK4 is most expressed in the testes, ...
G protein-coupled receptor kinase 2
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ...
GRK5
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ... GRK5 and the closely related GRK6 phosphorylate receptors at sites that encourage arrestin-mediated signaling rather than ...
G protein-coupled receptor kinase 3
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes ... Feng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI (June 2005). "ATP stimulates GRK-3 phosphorylation and beta-arrestin-2- ...
GPCR Signaling Regulation: The Role of GRKs and Arrestins
... Front Pharmacol. 2019 Feb 19;10:125. doi: 10.3389/fphar.2019.00125. ... In addition, GRKs and arrestins play a role in multiple signaling pathways in the cell, both GPCR-initiated and receptor- ... Here we focus on the mechanisms of GRK- and arrestin-mediated regulation of GPCR signaling, which includes homologous ... and subsequent binding of arrestin proteins, that selectively recognize active phosphorylated receptors. ...
Functionally Biased D2R Antagonists: Targeting the β-Arrestin Pathway to Improve Antipsychotic Treatment. | Broad Institute
Animals, Antipsychotic Agents, beta-Arrestins, Diagnostic Imaging, GTP-Binding Proteins, Humans, Locomotion, Mice, Receptors, ... At D2R, antipsychotic drugs antagonize both G-protein dependent (Gα) signaling and G-protein independent (β-arrestin) signaling ... Recent evidence from mouse genetic and pharmacological studies point to β-arrestin signaling as the major driver of ... Here, we characterize BRD5814, a highly brain penetrant β-arrestin biased D2R antagonist. BRD5814 demonstrated good target ...
Beta Arrestin 1 Antibody,Beta Arrestin 1 Peptide Suppliers & Manufacturers
Human Arrestin, beta 1 (ARRB1) Protein (Myc-DYKDDDDK Tag), Recombinant | ABIN2714946
Recombinant Arrestin, beta 1 (ARRB1) Protein (Myc-DYKDDDDK Tag). Spezies: Human. Quelle: HEK-293 Cells. Jetzt Produkt ... arrestin, beta 1, arrestin beta 1 L homeolog, beta-arrestin 1, putative beta-arrestin 1, ARRB1, arrb1, arrb1.L, CpipJ_ ... beta Arrestin 1 (ARRB1) (Arrestin, beta 1 (ARRB1)) Andere Bezeichnung Arrestin beta-1,arrb1 (ARRB1 Produkte) Synonyme arrb1, ... Target Alle beta Arrestin 1 (ARRB1) Proteine anzeigen beta Arrestin 1 (ARRB1) (Arrestin, beta 1 (ARRB1)) Protein-Typ ...
Beta-arrestin-2 regulates the development of allergic asthma. | [email protected]
Beta-arrestin-2 regulates the development of allergic asthma. ... Beta-arrestin-2 regulates the development of allergic asthma. ... is fully functional in mice lacking beta-arrestin-2. beta-arrestin-2-deficient mice demonstrate OVA-specific IgE responses, but ... Because beta-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, ... Here we show that allergen-sensitized mice having a targeted deletion of the beta-arrestin-2 gene do not accumulate T ...
Figures and data in ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression | eLife
Unique Properties of PathHunter® β-Arrestin Assays for GPCR Antagonist Discovery and Characterizatio
The PathHunter® Arrestin assay is unique among arrestin assays in that it preserves the one-to-one nature of arrestin binding ... The work presented here focuses on how this property of the PathHunter® Arrestin platform makes it ideal for the discovery and ... A common feature of 7TM receptors is that upon activation, the receptors are bound by cellular Arrestin proteins. DiscoveRx has ... Tools & Resources / Document Resource Library / Documents / Unique Properties of PathHunter® β-Arrestin Assays for GPCR ...
Monitoring of beta-arrestin recruitment to chemokine receptor heteromers,</em>...
Monitoring of beta-arrestin recruitment to chemokine receptor heteromers,. Ruth Seeber, Ethan See, Martina Kocan, Karin Eidne, ... Monitoring of beta-arrestin recruitment to chemokine receptor heteromers, / Seeber, Ruth; See, Ethan; Kocan, Martina et al. ... Seeber, R., See, E., Kocan, M., Eidne, K., & Pfleger, K. (2010). Monitoring of beta-arrestin recruitment to chemokine receptor ... Seeber, R, See, E, Kocan, M, Eidne, K & Pfleger, K 2010, Monitoring of beta-arrestin recruitment to chemokine receptor ...
beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased...
beta-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other ... In the present study we provide for the first time a mechanistic basis for the beta-arrestin function in Wnt/beta-catenin ... beta-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2 ... beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased ...
Beta Arrestin 1 Mouse anti-Human, Unconjugated, Clone: 1H8E4, Proteintech 150 μL Products
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Mouse Monoclonal Antibody Shop Beta Arrestin 1 Mouse anti-Human, Unconjugated, Clone: 1H8E4, Proteintech ... Beta Arrestin 1 Mouse anti-Human, Unconjugated, Clone: 1H8E4, Proteintech - ... The Beta Arrestin 1 antibody from Proteintech is a mouse monoclonal antibody generated with recombinant protein of human Beta ... The Beta Arrestin 1 antibody has been validated for the following applications: WB, ELISA analysis. ...
Reactome | Lysosome Destined Cargo:AP-1:beta-Arrestin-1:Vamp Complex [Golgi membrane]
Lysosome Destined Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin Complex [Golgi membrane] (Homo sapiens) ... Lysosome Destined Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin Complex [Golgi membrane] (Homo sapiens) ... Lysosome Destined Cargo:AP-1:beta-Arrestin-1:Vamp Complex [Golgi membrane] Stable Identifier ... Lysosome Destined Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin Complex [Golgi membrane] (Homo sapiens) ...
Arrestins | NIH 3D Print Exchange
Gentraget - Arrestin (Arr)
DI-fusion Usage statistics: The Bul1/2 Alpha-Arrestins Promote...
Recombinant Human B Arrestin 1 ARRB1
Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic...
... we demonstrate that both V2R-R137C and V2R-R137L mutants interact with beta-arrestins in an agonist-independent manner ... Animals, Arginine Vasopressin, Arrestins, Cell Line, Diabetes Insipidus, Nephrogenic, Humans, Hyponatremia, Inappropriate ADH ... Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic ... Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic ...
LinkLight™ U2-OS CCR6 / β-arrestin Cell Line | Bon Opus Biosciences
Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa | PLOS Genetics
c-h) Immunostaining of cone arrestin in WT (c-e) and heterozygous Clcc1 knockout (f-h) mice. The WT mice exhibit normal cone ... Dropout of cone cells is confirmed in Fig 9c-9h, where immunohistochemistry to cone arrestin displays ~half the cone density of ... Immunofluorescence assessment of mouse retinal cones by cone arrestin staining. Wax embedded tissue sections were kept at 37 °C ... Sections were incubated with cone arrestin (1:1000; Millipore, Germany) primary antibody reconstituted 1 × PBS containing 1% ...
β-arrestin - Not just for G protein-coupled receptors<...
β-arrestin - Not just for G protein-coupled receptors. / Spiegel, Allen.. In: Science, Vol. 301, No. 5638, 05.09.2003, p. 1338- ... β-arrestin - Not just for G protein-coupled receptors. Science. 2003 Sep 5;301(5638):1338-1339. doi: 10.1126/science.1089552 ... β-arrestin - Not just for G protein-coupled receptors. In: Science. 2003 ; Vol. 301, No. 5638. pp. 1338-1339. ... Spiegel, A. (2003). β-arrestin - Not just for G protein-coupled receptors. Science, 301(5638), 1338-1339. https://doi.org/ ...
Involvement of Beta-arrestin 1 and Beta-arrestin 2 in store operated calcium entry
... Autre titre : Implication de Beta-arrestin ... On the other hand, calcium imaging experiment in knocked down β-arrestin 1 or β-arrestin 2 in HEK 293 cells as well as HEK 293 ... En plus de Gα12 et Gα13, les protéines de désensibilisation des GPCR β -arrestin 1 et / ou β-arrestin 2 peuvent aussi activer ... The purpose of our study is to investigate the involvement of the proteins Gα12/13 and β-arrestin 1/β-arrestin 2 in the ...
Inhibition of chemoattractant N-formyl peptide receptor trafficking by active arrestins.
Furthermore, expression of arrestin-2 I386A/V387A/F388A but not arrestin-2 [1-382] inhibited recycling of the N-formyl peptide ... truncated arrestin-2 [1-382], and arrestin-2 I386A, V387A, F388A). Complexes between the N-formyl peptide receptor and active ... Inhibition of chemoattractant N-formyl peptide receptor trafficking by active arrestins. Academic Article * ... Recent studies have highlighted the emergence of a class of G protein-coupled receptors that are internalized in an arrestin- ...
Research Highlights
| Neuropsychopharmacology
PubPeer - Involvement of PKA/DARPP-32/PP1α and β- arrestin/Akt/GSK-3β...
UW students raise money to put AED in residence hall to save someone in cardiac arrest - In A Heartbeat
MDR - P2Y12 inhibitor Clinical Implications and Adverse Effects
CXCR7: a β-arrestin-biased receptor that potentiates cell migration and recruits β-arrestin2 exclusively through Gβγ subunits...
CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. SDF-1α also binds to its ... CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. SDF-1α also binds to its ... CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. SDF-1α also binds to its ... CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. SDF-1α also binds to its ...
Structural snapshots uncover a lock-and-key type conserved activation mechanism of β-arrestins by GPCRs | Sciety
Florida Police Arrest Woman For Domestic Nut Punching Incident | The Smoking Gun
ReceptorsProteinsARRB2ReceptorGPCRENDOCYTOSISKinasesPhosphorylationArrb1AntibodyInternalizationBindsActivationInteractionDownstreamCellsRoleBetaUniqueAlphaMouseRecruitmentGPCRsPathwayPathwaysKinaseBinding to phosphorylatedInteractionsActivateTranslocationPlasma membranePolyclonal antibodySignalingBovineInhibitMediatesMiceGRK2DopamineProteaseMoleculeBecoming phosphorylatedGeneBoundRegulationOverexpressionDistinctCompoundsExpressionAgonists
Receptors10
- A common feature of 7TM receptors is that upon activation, the receptors are bound by cellular Arrestin proteins. (discoverx.com)
- beta-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. (muni.cz)
- Arrestins (abbreviated Arr) are a family of proteins which are important in the regulation of signal transduction G-protein coupled receptors, which at first was discovered, as part of a conserved two step mechanism for regulating the activity of G protein-coupled receptors (GPCR) in rhodopsin visual system by Ursula Kuhn found Scott court, and β-called Global Martin J. Lohse system and kidney and colleagues. (arrestins.com)
- Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic syndrome of inappropriate antidiuresis. (ox.ac.uk)
- Spiegel, A 2003, ' β-arrestin - Not just for G protein-coupled receptors ', Science , vol. 301, no. 5638, pp. 1338-1339. (elsevier.com)
- Recent studies have highlighted the emergence of a class of G protein-coupled receptors that are internalized in an arrestin-independent manner. (unm.edu)
- These results indicate not only that a functional interaction between receptor and arrestin is required for recycling of certain G protein-coupled receptors, such as the N-formyl peptide receptor, but that the pattern of receptor phosphorylation further regulates this process. (unm.edu)
- Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a key determinant for the binding and activation of multifunctional regulatory proteins known as β-arrestins (βarrs). (sciety.org)
- Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. (nature.com)
- A beta-arrestin that functions similarly to BETA-ARRESTIN 1 in regulating signaling by G-PROTEIN-COUPLED RECEPTORS. (bvsalud.org)
Proteins3
- The signaling of most GPCRs via G proteins is terminated by the phosphorylation of active receptor by specific kinases (GPCR kinases, or GRKs) and subsequent binding of arrestin proteins, that selectively recognize active phosphorylated receptors. (nih.gov)
- A study from Nationwide Children's Hospital suggests that a newly identified group of proteins, alpha arrestins, may play a role in cell signaling that is crucial to new drug development. (news-medical.net)
- Lack of beta-arrestin signaling in the absence of active G proteins. (nih.gov)
ARRB22
- The present study explored the potential roles of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 (ARRB2) that are involved in the trafficking of DRD2 in patients with DSP. (dovepress.com)
- Arrestin 2 (ARRB2) Polymorphism is Associated With Adverse Consequences of Chronic Heroin Use. (cdc.gov)
Receptor13
- In addition, GRKs and arrestins play a role in multiple signaling pathways in the cell, both GPCR-initiated and receptor-independent. (nih.gov)
- GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of beta(arrestins), which prevents further receptor-G-protein coupling. (duke.edu)
- Inhibition of chemoattractant N-formyl peptide receptor trafficking by active arrestins. (unm.edu)
- In addition to demonstrating that the N-formyl peptide receptor belongs in this family, we have recently shown that recycling of the receptor requires the presence of arrestins. (unm.edu)
- To further elucidate mechanisms of arrestin-dependent regulation of G protein-coupled receptor processing, we examined the effects of altering the receptor-arrestin complex on ternary complex formation and cellular trafficking of the N-formyl peptide receptor by studying two active arrestin-2 mutants (truncated arrestin-2 [1-382], and arrestin-2 I386A, V387A, F388A). (unm.edu)
- Complexes between the N-formyl peptide receptor and active arrestins exhibited higher affinity in vitro than the complex between the N-formyl peptide receptor and wild-type arrestin and furthermore were observed in vivo by colocalization studies using confocal microscopy. (unm.edu)
- To assess the effects of these altered interactions on receptor trafficking, we demonstrated that active, but not wild-type, arrestin expression retards N-formyl peptide receptor internalization. (unm.edu)
- Furthermore, expression of arrestin-2 I386A/V387A/F388A but not arrestin-2 [1-382] inhibited recycling of the N-formyl peptide receptor, reflecting an expanded role for arrestins in G protein-coupled receptor processing and trafficking. (unm.edu)
- [ 89 ] Exposure to bacterial LPS decreases membrane expression of CCR8 on DCs possibly by receptor internalization through β-arrestin. (medscape.com)
- Receptor interaction with b-arrestin is an important regulatory key element in the termination of G-protein-dependent receptor signalling. (uniklinikum-jena.de)
- The interaction of a GPCR and β-arrestin is regulated by ligand binding and receptor phosphorylation by specific receptor kinases. (uniklinikum-jena.de)
- Since β-arrestins not only turn off G-protein-dependent-signalling but represent starting points for novel signalling cascades, we are also interested to investigate receptor ligands which are able to discriminate between G-protein and β-arrestin mediated receptor signalling. (uniklinikum-jena.de)
- The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling. (krakow.pl)
GPCR5
- Here we focus on the mechanisms of GRK- and arrestin-mediated regulation of GPCR signaling, which includes homologous desensitization and redirection of signaling to additional pathways by bound arrestins. (nih.gov)
- DiscoveRx has pioneered the PathHunter ® β-Arrestin assay platform for monitoring these events using enzyme fragment complementation (EFC) and applied this technique to develop assays for more than 170 human GPCR targets. (discoverx.com)
- Unlike second messenger assays that are amplified through downstream signaling events, each arrestin protein binds to a single activated GPCR. (discoverx.com)
- The work presented here focuses on how this property of the PathHunter ® Arrestin platform makes it ideal for the discovery and characterization of GPCR antagonists. (discoverx.com)
- En plus de Gα12 et Gα13, les protéines de désensibilisation des GPCR β -arrestin 1 et / ou β-arrestin 2 peuvent aussi activer RhoA. (usherbrooke.ca)
ENDOCYTOSIS1
- The Bul1/2 Alpha-Arrestins Promote Ubiquitylation and Endocytosis of the Can1 Permease upon Cycloheximide-Induced TORC1-Hyperactivation. (ac.be)
Kinases2
- Finally, we show that beta-arrestin interacts with PtdIns kinases PI4KII alpha and PIP5KI beta. (muni.cz)
- We propose that beta-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P-2, which is produced locally upon Wnt3a stimulation by beta-arrestin- and Dishevelled-associated kinases. (muni.cz)
Phosphorylation3
- We demonstrate that beta-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. (muni.cz)
- beta-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2)-binding protein Amer1/WTX/Fam123b. (muni.cz)
- In summary, our data show that beta-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. (muni.cz)
Arrb12
- Recombinant human Arrestin beta-1 / ARRB1 (transcript variant 2) protein expressed in HEK293 cells. (antikoerper-online.de)
- Recombinant Human B Arrestin 1_ARRB1 is available at Genprice in USA and Gentaur in Europe. (genprice.shop)
Antibody2
- The Beta Arrestin 1 antibody from Proteintech is a mouse monoclonal antibody generated with recombinant protein of human Beta Arrestin 1. (fishersci.no)
- The Beta Arrestin 1 antibody has been validated for the following applications: WB, ELISA analysis. (fishersci.no)
Internalization1
- Using bioluminescence resonance energy transfer and confocal microscopy, we demonstrate that both V2R-R137C and V2R-R137L mutants interact with beta-arrestins in an agonist-independent manner resulting in dynamin-dependent internalization. (ox.ac.uk)
Binds1
- CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. (elsevier.com)
Activation1
- Upon T cell activation of human peripheral blood T cells, we found that the majority of cAMP was generated in T cell lipid rafts followed by activation of protein kinase A. However, upon TCR and CD28 coligation, beta-arrestin in complex with cAMP-specific phosphodiesterase 4 (PDE4) was recruited to lipid rafts which down-regulated cAMP levels. (ox.ac.uk)
Interaction1
- Des études de co-immunoprécipitation démontrent une interaction entre la β-arrestin 1 et STIM1, alors qu'aucune interaction n'a été observée entre les β-arrestin 1 et Orai1. (usherbrooke.ca)
Downstream1
- Using fluorescence recovery after photobleaching we show here that beta-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. (muni.cz)
Cells1
- Importantly, cells lacking beta-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. (muni.cz)
Role1
- Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons. (nih.gov)
Beta7
- Dieses beta Arrestin 1 Protein ist gelabelt mit Myc-DYKDDDDK Tag. (antikoerper-online.de)
- In the present study we provide for the first time a mechanistic basis for the beta-arrestin function in Wnt/beta-catenin signaling. (muni.cz)
- Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice. (duke.edu)
- Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. (duke.edu)
- arrestin, and mitragynines no This distinction is important because beta-arrestin activity is associated with the dangerous side effects of opioids, including slow, shallow breathing that cannot sustain life. (justicenewsflash.com)
- Beta-arrestina que funciona de forma similar a la BETA-ARRESTINA 1 en la regulación de la señalización mediante RECEPTORES ACOPLADOS A PROTEÍNAS G. Se expresión es alta en el sistema nervioso central donde puede regular la señalización mediante RECEPTORES SINÁPTICOS. (bvsalud.org)
- Conversely, overexpression of either PDE4 or beta-arrestin augmented TCR/CD28-stimulated cytokine production. (ox.ac.uk)
Unique1
- The PathHunter ® Arrestin assay is unique among arrestin assays in that it preserves the one-to-one nature of arrestin binding and directly translates the binding events to signal generation. (discoverx.com)
Alpha1
- DI-fusion Usage statistics: The Bul1/2 Alpha-Arrestins Promote. (ac.be)
Mouse1
- Recent evidence from mouse genetic and pharmacological studies point to β-arrestin signaling as the major driver of antipsychotic efficacy and suggest that a β-arrestin biased D2R antagonist could achieve an additional level of selectivity at D2R, increasing the therapeutic index of next generation antipsychotics. (broadinstitute.org)
Recruitment11
- For GPCRs, ligand-induced β-arrestin recruitment activates signaling cascades independent of G-protein signaling to provide a nonamplified signal which is ideal for antagonist mode screening, ligand pharmacology analysis, and GPCR deorphanization. (discoverx.com)
- The recruitment of arrestins to activated 7TMRs results in the activation of alternative signaling pathways, quenching of G-protein activation, and coupling to clathrin-mediated endocytosis. (discoverx.com)
- This chapter discusses the utility and methods involved in using the PathHunter β-galactosidase complementation system to monitor arrestin recruitment and the advantages of exploiting this pathway in the characterization of 7TMR function. (discoverx.com)
- Here, we evaluate μOR trafficking in response to activation by a novel μ-selective agonist derived from the naturally occurring plant product, salvinorin A. It is interesting that this compound, termed herkinorin , does not promote the recruitment of β-arrestin-2 to the μOR and does not lead to receptor internalization. (aspetjournals.org)
- Administration of a single isolated serine protease from Alternaria, Alternaria alkaline serine protease (AASP), was sufficient to fully activate PAR 2 signaling and induce β-arrestin-2 / -dependent eosinophil and lymphocyte recruitment in vivo. (arizona.edu)
- MRAP2 inhibits β-arrestin recruitment to the ghrelin receptor by preventing GHSR1a phosphorylation. (wjgnet.com)
- The latter is often assumed to be nonbiased, or balanced, and usually produces efficient activation of the most measured signaling outputs, normally G protein activation and arrestin recruitment. (aspetjournals.org)
- G protein by Ca 2+ flux and β-arrestin recruitment, hence allowing biased activity studies. (innoprot.com)
- Functional [small beta]-arrestin recruitment assays were used to determine equilibrium dissociation constants (Kb) and showed that all of the tested SF5 and CF3 compounds are CB1 neutral antagonists. (sinapse.ac.uk)
- 346 - Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein - Proc. (nih.gov)
- This compound was confirmed to be selective for the μ opioid receptor and preferentially activated the G-protein signaling with little β-arrestin recruitment. (nih.gov)
GPCRs7
- Arrestins play a key role in controlling the activity and signal transduction of GPCRs inside the cells of the body. (technologynetworks.com)
- The researchers' close observation of the interactions between arrestins and GPCRs yielded crucial conclusions. (technologynetworks.com)
- Different arrestins (visual arrestin (or Arrestin 1), beta-arrestin 1 (or Arrestin 2) and beta-arrestin 2 (or Arrestin 3) can reduce the activity of their target GPCRs in several different ways. (chemeurope.com)
- Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs. (nih.gov)
- This strategy may facilitate the structure-guided design of arrestin-biased ligands at other GPCRs, including polypharmacological biased ligands. (nih.gov)
- In addition, GPCRs have also been found to signal through arrestin-mediated cascades. (frontiersin.org)
- MPX NOMAD Cells are cell lines stably co-expressing tag-free GPCRs and two Nomad Biosensors to monitor G-protein and β-arrestin modulation. (innoprot.com)
Pathway10
- This study aimed to elucidate the regulation of β-arrestin 1/2 on podocyte apoptosis through the Wnt/b-catenin pathway. (medscimonit.com)
- Up-regulated β-arrestin 1/2 promoted podocyte apoptosis and p53 pathway by increasing Bax, cleaved caspase-3, and p-p53 levels in high-glucose-induced podocytes. (medscimonit.com)
- Expression of β-catenin was increased in the β-arrestin 1/2 up-regulated group, which indicated that the Wnt/b-catenin pathway was activated. (medscimonit.com)
- Wnt/b-catenin pathway inhibitor (Dkk1) distinctly suppressed the apoptosis induced by β-arrestin 1/2 overexpression and high glucose. (medscimonit.com)
- These results provide a molecular pathomechanism of β-arrestin 1/2 and Wnt/β-catenin pathway on podocyte apoptosis and provide new ideas for the treatment of diabetic nephropathy, which paves the way for the future study of diabetic nephropathy and podocytes. (medscimonit.com)
- 15. KISS1R signals independently of Gαq/11 and triggers LH secretion via the β-arrestin pathway in the male mouse. (nih.gov)
- One emerging strategy to address the opioid crisis is the development of mu opioid receptor (MOR) ligands that preferentially signal the G-protein vs. β-arrestin pathway. (rti.org)
- These effects of Istradefylline were reduced by the knockdown of A2AR but independent of A2AR-mediated G protein- or β-arrestin-dependent signal pathway. (nih.gov)
- The authors of this study hypothesized that if a molecule could interact with the μ opioid receptor and activate the G-protein but not the β-arrestin pathway it would provide the pain relief of opioids, without the negative side effects. (nih.gov)
- The authors then synthesized modified versions of some of these compounds to enhance binding to the μ opioid receptor and arrived at a compound that strongly bound the μ opioid receptor (but not the κ opioid receptor) and activated the G-protein signaling pathway but not the β-arrestin pathway. (nih.gov)
Pathways4
- Arrestins can also activate numerous signaling pathways. (nih.gov)
- Some of the side effects that occur with certain medicines (such as morphine-based drugs) are the result of arrestin-dependent signaling pathways. (technologynetworks.com)
- C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways. (harvard.edu)
- 8. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. (nih.gov)
Kinase7
- Using permanent and primary human bronchial epithelial (HBE) cells at air-liquid interface, we show that DEPs activate the human MMP-1 gene via RAS and subsequent activation of RAF-MEK-ERK1/2 mitogen-activated protein kinase signaling, which can be scaffolded by β-arrestins. (nih.gov)
- The function of beta-arrestin in the nucleus is not yet well understood, even if some data indicate clearly that beta-arrestin enters and exit the nucleus to take out from there some of its partners like the kinase JNK3 or the ubiquitin ligase Mdm2. (chemeurope.com)
- Beta-arrestin 2, for example, is responsible for the downregulation of β-Adrenergic receptor which is phosphorylated by the β-adrenergic receptor kinase, thyrotropin releasing hormone receptor (TRHR), C5a Receptor (C5aR), AngiotensinII receptor. (chemeurope.com)
- Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and β-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. (elsevier.com)
- 6. Expression and regulation of G protein-coupled receptor kinase 5 and beta-arrestin-1 in rat thyroid FRTL5 cells. (nih.gov)
- The interaction can be triggered by protein activation/inactivation and is the basis of several DiscoveRx cell based assays including the Arrestin and the Kinase assays. (discoverx.com)
- Genetic association between G protein-coupled receptor kinase 6/ß-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia. (cdc.gov)
Binding to phosphorylated1
- Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. (nih.gov)
Interactions2
- Our approach provides a template for generating arrestin-biased ligands by modifying predicted ligand interactions that block TM5 interactions and promote EL2 interactions. (nih.gov)
- Such projects include investigating receptor structure/function/pharmacology relationships, receptor-effector coupling mechanisms, G protein and beta-arrestin interactions, and molecular mechanisms of receptor desensitization and intracellular trafficking. (nih.gov)
Activate3
- Therefore, drugs that can activate the receptor without recruiting the arrestins may be a promising step in the development of opiate analgesics that distinguish between agonist activity and receptor regulation and may ultimately lead to therapeutics designed to provide pain relief without the adverse side effects normally associated with the opiate narcotics. (aspetjournals.org)
- In most cases agonists regarded as nonbiased can efficiently activate both G protein- and arrestin-dependent signaling. (aspetjournals.org)
- Relative to this, biased agonists preferentially activate either G protein- or arrestin-dependent signaling as shown in bold arrows. (aspetjournals.org)
Translocation5
- In this study, the involvement of microtubules and microfilaments in the light-driven translocation of arrestin and transducin was investigated. (arvojournals.org)
- Quantitative confocal imaging was used to assess the impact of these treatments on arrestin and transducin translocation. (arvojournals.org)
- Perturbation of the microtubule cytoskeleton with thiabendazole slowed the translocation of both arrestin and transducin, but only in moving from the outer to the inner segments. (arvojournals.org)
- Transgenic Xenopus expressing fusions of green fluorescent protein (GFP) with portions of arrestin implicates the C terminus of arrestin as an important portion of the molecule for promoting translocation. (arvojournals.org)
- The results show that disruption of the cytoskeletal network in rod photoreceptors has specific effects on the translocation of arrestin and transducin. (arvojournals.org)
Plasma membrane1
- Previous studies show that β-arrestin signaling and receptor endocytosis are modulated by the plasma membrane phosphoinositide lipid phosphatidylinositol-(4, 5)-bisphosphate (PI(4,5)P 2 ). (pnas.org)
Polyclonal antibody1
- Arrestin antibody LS-C752710 is an unconjugated rabbit polyclonal antibody to human Arrestin (SAG). (lsbio.com)
Signaling12
- The nearly ubiquitous involvement of arrestin in 7TMR signaling has spurred the development of several methods for monitoring this interaction in mammalian cells. (discoverx.com)
- We identified specific amino acid-ligand contacts at transmembrane helix 5 (TM5) and extracellular loop 2 (EL2) responsible for Gi/o and β-arrestin signaling, respectively, and targeted those residues to develop biased ligands. (nih.gov)
- A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. (elsevier.com)
- These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling. (elsevier.com)
- We sought to determine whether Alternaria-induced PAR 2 signaling contributed to asthma symptoms via a PAR 2 /β-arrestin signaling axis, identify the protease activity responsible for PAR 2 signaling, and determine whether protease activity was sufficient for Alternaria-induced asthma symptoms in animal models. (arizona.edu)
- We initially used in vitro models to demonstrate Alternaria-induced PAR 2 /β-arrestin-2 signaling. (arizona.edu)
- In conclusion, Alternaria filtrates induce airway inflammation and mucus hyper-plasia largely via AASP using the PAR 2 /β-arrestin signaling axis. (arizona.edu)
- 21: Deubiquitinases and Their Emerging Roles in β-Arrestin-mediated Signaling. (gale.com)
- 2. β-Arrestin 1 in Thyrotropin Receptor Signaling in Bone: Studies in Osteoblast-Like Cells. (nih.gov)
- 10. Distinct and shared roles of β-arrestin-1 and β-arrestin-2 on the regulation of C3a receptor signaling in human mast cells. (nih.gov)
- β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling. (nih.gov)
- Research focused on the mapping of a receptor/G protein interface and a receptor dimer interface, and the investigation of the physiological roles of G protein-dependent versus β-arrestin-dependent signaling in hepatocytes. (nih.gov)
Bovine1
- In the same issue of Nature , a team led by researchers in Germany published the structure of another arrestin from the bovine eye called arrestin p44. (nih.gov)
Inhibit2
- We demonstrate that β-arrestins interact directly with FAK and inhibit its autophosphorylation in resting cells. (inserm.fr)
- Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. (anticorps-enligne.fr)
Mediates1
- 1. β-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation. (nih.gov)
Mice4
- Studies in mice have shown that β-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression. (aspetjournals.org)
- Alternaria filtrates were then used to sensitize and challenge wild-type, PAR 2 / and β-arrestin-2 / mice in vivo. (arizona.edu)
- Intranasal administration of Alternaria filtrate resulted in a protease-dependent increase of airway inflammation and mucin production in wild-type but not PAR 2 / or β-arrestin-2 / mice. (arizona.edu)
- Degroot G , Lepage V, Parmentier M, Springael J. The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking. (wjgnet.com)
GRK25
- Our aim was to characterize GRK2 and β-arrestins expression in different pituitary adenomas and to investigate their potential role in the response to somatostatin analog (SSA) treatment in GH-secreting adenomas (GHomas). (elsevier.com)
- 0001). SSA treatment did not affect GRK2 and β-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. (elsevier.com)
- 05). In conclusion, for the first time, we characterized GRK2, β-arrestin 1, and β-arrestin 2 expression in a representative number of pituitary adenomas. (elsevier.com)
- β-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment. (elsevier.com)
- 19. GRK2 and beta-arrestin 1 as negative regulators of thyrotropin receptor-stimulated response. (nih.gov)
Dopamine2
Protease1
- This parental cell line stably expresses a beta-arrestin/TEV protease fusion protein and the beta-lactamase ( bla ) reporter gene under the control of a UAS response element. (thermofisher.com)
Molecule1
- Using single-molecule fluorescence resonance energy transfer imaging, we show that β-arrestin is strongly autoinhibited in its basal state. (nih.gov)
Becoming phosphorylated1
- In another branch, the receptor becomes desensitized by becoming phosphorylated, bound to β-arrestin, and internalized by clathrin-coated pits. (pnas.org)
Gene2
- In the nucleus, it has also been described that beta arrestins are also able to modify gene expression, by enhancing transcription of some specific genes. (chemeurope.com)
- Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia. (cdc.gov)
Bound2
- They thus searched for a synthetic antibody fragment that could stabilize β-arrestin-1 in its active state bound to a segment of the receptor. (nih.gov)
- Once arrestin is bound to the receptor it is unable to signal further. (chemeurope.com)
Regulation2
- Although β-arrestins (ARRBs) regulate diverse physiological and pathophysiological processes, their functions and regulation in Parkinson's disease (PD) remain poorly defined. (elsevier.com)
- Nevertheless, the potential mechanism of β-arrestins on the regulation of podocyte apoptosis has rarely been discussed. (medscimonit.com)
Overexpression1
- β-arrestin 1/2 overexpression inhibited the expression of nephrin and podocin protein. (medscimonit.com)
Distinct2
- Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. (elsevier.com)
- Its engagement with a phosphopeptide mimicking phosphorylated receptor tail efficiently releases the β-arrestin tail from its N domain to assume distinct conformations. (nih.gov)
Compounds2
Expression4
- β-Arrestin 1 expression was low in all 3 adenoma histotypes. (elsevier.com)
- This study structured β-arrestin 1/2 down-regulated and up-regulated expression by plasmid transfection. (medscimonit.com)
- β-arrestin 1/2 expression levels of podocytes were up-regulated in high-glucose-induced podocytes. (medscimonit.com)
- 13. Expression of beta-arrestins in toxic and cold thyroid nodules. (nih.gov)
Agonists1
- This led to the key concept-which has dominated the opioid field now for almost 20 years-that the analgesic effects of μ -receptor agonists are G protein-mediated, and the adverse effects (constipation and respiratory depression) as well as tolerance, are mediated in the main by arrestin-3. (aspetjournals.org)