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
Fatigue
Databases, Protein
Sequence Analysis, Protein
Systems Integration
Internet
Sequence Alignment
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Melanesia
The collective name for the islands of the Pacific Ocean northeast of Australia, including NEW CALEDONIA; VANUATU; New Hebrides, Solomon Islands, Admiralty Islands, Bismarck Archipelago, FIJI, etc. Melanesia (from the Greek melas, black + nesos, island) is so called from the black color of the natives who are generally considered to be descended originally from the Negroid Papuans and the Polynesians or Malays. (From Webster's New Geographical Dictionary, 1988, p748 & Room, Brewer's Dictionary of Names, 1992, p344)
Anopheles gambiae
Algorithms
Entomology
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Retina
The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.
Hominidae
Cone Opsins
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Genetics
Drosophila
Drosophila melanogaster
Drosophila Proteins
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
Limb-girdle muscular dystrophy
Arrestin. *Oguchi disease 1. Myelin. *Pelizaeus-Merzbacher disease. *Dejerine-Sottas disease. *Charcot-Marie-Tooth disease 1B, ...
Charcot-Marie-Tooth disease
Arrestin. *Oguchi disease 1. Myelin. *Pelizaeus-Merzbacher disease. *Dejerine-Sottas disease. *Charcot-Marie-Tooth disease 1B, ...
CLTC
1997). "Arrestin/clathrin interaction. Localization of the arrestin binding locus to the clathrin terminal domain". J. Biol. ...
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 photoreceptor protein that is involved in desensitization of the ... 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 Zyklophin - selective peptide antagonist; dynorphin A analogue Found in numerous species of mint, ( ... β-arrestin antagonist Tifluadom - (atypical) benzodiazepine Nalfurafine (Remitch), which was introduced in 2009, is the first ... β-arrestin antagonist Amentoflavone - non-selective; naturally-occurring AT-076 - non-selective, likely long acting; JDTic ...
Denis Baylor
"Prolonged photoresponses in transgenic mouse rods lacking arrestin". Nature. 389 (6650): 505-509. Bibcode:1997Natur.389..505X. ...
Herkinorin
Unlike most μ-opioid agonists, herkinorin does not promote the recruitment of β-arrestin-2 to the intracellular domain of the μ ... 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 ...
Trevena Inc
While it binds to the same receptors as opioid analgesics, TRV734 has very weak β-arrestin recruitment, unlike other available ... Violin, Jonathan D.; Lefkowitz, Robert J. (2007). "Β-Arrestin-biased ligands at seven-transmembrane receptors". Trends in ... ß-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: A novel therapeutic ... but Trevaga hopes to avoid this with TRV250 by bypassing the β-arrestin pathway. TRV734 is an oral follow-up to the injected ...
Neurotensin receptor 1
"Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes ... "Discovery of ML314, a Brain Penetrant Non-Peptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor". ACS Med Chem ...
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 ...
AP3B1
Kim YM, Barak LS, Caron MG, Benovic JL (May 2002). "Regulation of arrestin-3 phosphorylation by casein kinase II". The Journal ...
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
"GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling". Cell. 166 (4): 907-919. doi:10.1016/j.cell. ...
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 ...
GPR3
... however this result was not confirmed in a β-arrestin recruitment assay. Mice lacking GPR3 were found to develop late-onset ... "Lipid G Protein-coupled Receptor Ligand Identification Using β-Arrestin PathHunter™ Assay". J. Biol. Chem. 284 (18): 12328-38. ...
Smoothened
"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2". Science. 306 (5705): 2257-60. Bibcode: ...
Hedgehog signaling pathway
"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2". Science. 306 (5705): 2257-60. doi: ...
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 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 ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ... GRK/arrestin system serves as a signaling switch for G protein-coupled receptors. GRK4 is most highly 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 ...
Arrestin - Wikipedia
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 between two GPCRs available ... Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, after ...
Arrestin-like, N-terminal (IPR011021) | InterPro | EMBL-EBI
Arrestin-like, N-terminal (IPR011021). Short name: Arrestin-like_N Overlapping homologous superfamilies *Arrestin, N-terminal ( ... Arrestins comprise a family of closely-related proteins that includes beta-arrestin-1 and -2, which regulate the function of ... The arrestin superfamily: cone arrestins are a fourth family.. FEBS Lett. 362 247-55 1995 ... Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family.. J. Biol. Chem. 267 17882-90 1992 ...
Arrestin beta 2 - Wikipedia
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-related proteins mediate pH signaling in fungi | PNAS
... human arrestin β1 (arrB), and bovine visual arrestin (arrV) and the consensi for arrestin N-terminal and C-terminal PFAM ... Here we show that PalF is a non-metazoan arrestin-related protein, as verified by (i) the presence of arrestin N- and C- ... Conservation of the PalF family arrestin N-terminal and C-terminal domains. Shown above are positions of the PalF PFAM arrestin ... for amino acid sequences are P08168 (bovine visual arrestin), P49407 (human β1 arrestin), P78612 and Q9P904 (A. nidulans PalF ...
Arrestin C-terminal-like domain (IPR011022) | InterPro | EMBL-EBI
The arrestin superfamily: cone arrestins are a fourth family.. FEBS Lett. 362 247-55 1995 ... Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family.. J. Biol. Chem. 267 17882-90 1992 ... This domain is found in arrestins and in other proteins including arrestin domain-containing proteins, protein ROD1 [PMID: ... Cone photoreceptors C-arrestin (arrestin-X) [PMID: 7720881], which could bind to phosphorylated red/green opsins; and ...
RCSB PDB - Gene View
- ARRDC3 - arrestin domain containing 3
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Diversifying Role for β-Arrestin | Science Signaling
show that β-arrestins, which limit signaling by GPCRs coupled to G proteins of the Gs class, serve a very similar function in ... E. F. Grady, β-Arrestin, a two-fisted terminator. Science 315, 605-606 (2007). [Summary] [Full Text] ... Targeting of diacylglycerol degradation to M1 muscarinic receptors by β-arrestins. Science 315, 663-666 (2007). [Abstract] [ ...
Arrestin C domain-containing protein - Anopheles farauti
IPR011021 Arrestin-like_N. IPR014752 Arrestin_C. IPR011022 Arrestin_C-like. IPR017864 Arrestin_CS. IPR014753 Arrestin_N. ... IPR011021 Arrestin-like_N. IPR014752 Arrestin_C. IPR011022 Arrestin_C-like. IPR017864 Arrestin_CS. IPR014753 Arrestin_N. ... Arrestin_C domain-containing proteinInterPro annotation. ,p>Information which has been generated by the UniProtKB automatic ... tr,A0A182QD30,A0A182QD30_9DIPT Arrestin_C domain-containing protein OS=Anopheles farauti OX=69004 PE=4 SV=1 ...
β-Blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation | PNAS
Both β-Arrestin 1 and β-Arrestin 2 Are Required for Alp- or Car-Induced ERK Activation.. To determine if Alp or Car stimulation ... In our experiments, we show that both Alp and Car use β-arrestin to induce β1AR-mediated EGFR transactivation. As β-arrestin is ... siRNA Experiments Targeting β-Arrestins.. siRNA targeting β-arrestins were generated and the sequence of the 21-nt siRNAs has ... In contrast, ERK activation was significantly blocked in the presence of siRNA targeting β-arrestin 1, β-arrestin 2, or both ...
JCI -
Hepatic β-arrestin 2 is essential for maintaining euglycemia
Insulin-induced phosphorylation of AKT and GSK3α/β remains unaffected by the lack of β-arrestin 2 in hepatocytes. Primary ... Our data support the concept that strategies aimed at enhancing hepatic β-arrestin 2 activity could prove useful for ... Adult mice lacking β-arrestin 1 selectively in hepatocytes did not show any changes in glucose homeostasis. Importantly, ... However, hepatocyte-specific β-arrestin 2 deficiency did not affect hepatic insulin sensitivity or β-adrenergic signaling. ...
JCI -
Hepatic β-arrestin 2 is essential for maintaining euglycemia
Interestingly, hepatic β-arrestin 1, in contrast with β-arrestin 2, does not play a role in regulating hepatic GCGR activity ... The activity of almost all GPCRs is modulated by a pair of proteins known as β-arrestin 1 and 2 (also known as arrestin 2 and 3 ... To address this issue, we generated and analyzed mutant mice that lack β-arrestin 2 (Arrb2) or β-arrestin 1 (Arrb1) selectively ... GCGR internalization is abolished in hepatocytes lacking β-arrestin 2. To examine whether β-arrestin 2 is required for the ...
Arrestin-mediated endocytosis of yeast plasma membrane transporters
It also reveals functional redundancy between arrestins and the arrestin-like adaptors Bul1 and Bul2. In addition, we show that ... analysis is complicated by redundancy amongst the arrestins. We have tested this model by removing all the arrestins and ... Arrestin-mediated endocytosis of yeast plasma membrane transporters Traffic. 2009 Dec;10(12):1856-67. doi: 10.1111/j.1600- ... As yeast contains a large family of arrestins, this has been suggested as a general model for transporter regulation; however, ...
Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors. - PubMed - NCBI
Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.. Reiter E1, Ahn S, Shukla AK, Lefkowitz RJ. ... Pluridimensionality of β-arrestin-dependent signaling at seven-transmembrane receptor (7TMRs). Some of the best-characterized β ... Relative activities of the nine ligands for G protein activation (G prot), β-arrestin recruitment (β-arr), and extracellular ... A general model for β-arrestin-biased ligand mechanism of action is proposed (, , ). GRK2/3 and GRK5/6 exert qualitatively ...
Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide | Nature
... the structure of the complex shows striking conformational differences in β-arrestin-1 when compared w… ... The crystal structure of β-arrestin-1 in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived ... Here we report the crystal structure of β-arrestin-1 (also called arrestin-2) in complex with a fully phosphorylated 29-amino- ... An additional phosphate-binding element in arrestin molecule. Implications for the mechanism of arrestin activation. . J. Biol ...
arrestin - definition and meaning
You vont think o arrestin your own son for the money, and sendin him off to the Fleet, will you, you unnatral wagabone? ... In a human study, the same scientists found that beta-arrestin-1 levels were low in the blood cells of depressed patients but ... Boy takes a grab at yo money, an if deys any lef , you gives it to a policeman fo arrestin him. ... MCSO is not going to each house in a neighborhood, kicking down doors, and arrestin whomever they run into. ...
ARR3 - Arrestin-C - Homo sapiens (Human) - ARR3 gene & protein
IPR000698. Arrestin. IPR011021. Arrestin-like_N. IPR011022. Arrestin_C-like. IPR017864. Arrestin_CS. IPR014753. Arrestin_N. ... IPR000698. Arrestin. IPR011021. Arrestin-like_N. IPR011022. Arrestin_C-like. IPR017864. Arrestin_CS. IPR014753. Arrestin_N. ... Belongs to the arrestin family.Curated. Phylogenomic databases. evolutionary genealogy of genes: Non-supervised Orthologous ... sp,P36575,ARRC_HUMAN Arrestin-C OS=Homo sapiens GN=ARR3 PE=1 SV=2 MSKVFKKTSSNGKLSIYLGKRDFVDHVDTVEPIDGVVLVDPEYLKCRKLFVMLTCAFRYG ...
The arrestin superfamily: cone arrestins are a fourth family
The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin i … ... Arrestins constitute a superfamily of regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, ... The arrestin superfamily: cone arrestins are a fourth family FEBS Lett. 1995 Apr 3;362(2):247-55. doi: 10.1016/0014-5793(95) ... The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin in Xenopus ...
Cone Arrestin Expression and Induction in Retinoblastoma Cells | SpringerLink
The arrestin superfamily includes visual arrestins, beta-arrestins (βarrestins) and insect... ... Arrestins are regulatory proteins that down-regulate phosphorylated G-protein coupled receptors (GPCRs). ... rod arrestin (also known as S-antigen or Arrestin 1) and cone arrestin (X-arrestin or Arresting. Rod arrestin was the first ... The arrestin superfamily includes visual arrestins, beta-arrestins (βarrestins) and insect chemosensory arrestins. Two members ...
Recombinant Human Arrestin C protein (ab116769) Protocols
Anti-Beta Arrestin 2 antibody (ab151774) | Abcam
Rabbit polyclonal Beta Arrestin 2 antibody. Validated in WB, IHC and tested in Rat, Human. Cited in 2 publication(s). Immunogen ... Anti-Beta Arrestin 2 antibody. See all Beta Arrestin 2 primary antibodies. ... also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin- ... All lanes : Anti-Beta Arrestin 2 antibody (ab151774) at 0.5 µg/ml. Lane 1 : HeLa Whole Cell Lysate. Lane 2 : Rat Skeletal ...
Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling. - PubMed - NCBI
The global scope of the β-arrestin interactome and β-arrestin dependent phosphorylation events. (a) Subcellular and (b) ... c) Novel roles of β-arrestins as endocytosis adaptors, E3 ubiquitin ligase adaptors and the new paradigm of β-arrestin ... The protein highlighted in red and outlined in green were present in both, the β-arrestin interactome and the β-arrestin ... Please note that the different binding partners of β-arrestins shown in the figure probably do not bind β-arrestins ...
Role of the Drosophila Non-Visual ß-Arrestin Kurtz in Hedgehog Signalling
Consistently, β-arrestins play important roles during vertebrate development and are implicated in a variety of human ... Here we take advantage of the fruit fly model to analyse the genetic requirements of the unique fly non-visual β-arrestin ( ... The activity of β-arrestins is generally linked to seven-transmembrane receptors, but in vertebrates they can also participate ... Our data suggest that insect epithelial cells have evolved arrestin-independent mechanisms to control receptor turnover and ...
Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2 | Science
JCI -
β Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion
β-Arrestin 1 and 2 (Barr1 and Barr2, respectively) are intracellular signaling molecules that regulate many important metabolic ... β Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion. ... β Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion. ...
kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila | Genetics
kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila ...
Beta]-arrestins : traffic cops of cell signaling (VHS tape, 2002) [WorldCat.org]
... arrestins : traffic cops of cell signaling. [Robert J Lefkowitz; National Institutes of Health (U.S.). Medical Arts and ... Photography Branch.;] -- (Producer) Discusses the diversity of roles played by the beta-arrestins in regulating the function ... Arrestins a schema:Intangible ;. schema:name "Arrestins"@en ;. . ... Beta]-arrestins : traffic cops of cell signaling. Author:. ... schema:name "[Beta]-arrestins : traffic cops of cell signaling"@en ;. schema:productID "50684982" ;. schema:publication
Transduction of Receptor Signals by ß-Arrestins | Science
arrestin beta 2 L homeolog ELISA Kits | Biocompare.com
Compare arrestin beta 2 L homeolog ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, ... arrestin beta 2 L homeolog ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a widely used application for detecting ... Your search returned 5 arrestin beta 2 L homeolog ELISA ELISA Kit across 1 supplier. ...
Arrestin-S ELISA Kits from AMSBIO LLC | Biocompare.com
Arrestin
Summary Report | CureHunter
Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental ... Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. ... Arrestin. Subscribe to New Research on Arrestin A 48-Kd protein of the outer segment of the retinal rods and a component of the ... Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental ...
ProteinsReceptorsBeta-arrestinsGPCRsGPCRPhosphorylationInteractionAntibodyRegulatePhotoreceptorsEndocytosisInternalizationGRKsRole of arrestinBindVisual arrestinsRhodopsinPathwaysGeneARRB2BovineAssayRetinal S-antigenRecruitmentMolecularProtein-coupled receptor kinaseConformationResiduesKinasesSuperfamilyRegulationKinasePlasma membraneAdaptorsDesensitizationSpecificityMammalianUbiquitinationThioredoxin-interacActivationAntibodiesARR3KnockdownMediateLocalizationERK1ARRDC3AdditionallyInducesHuman Beta ArrestinDownstreamSignalingSiRNA
Proteins51
- The N-terminal domain consists of an immunoglobulin-like beta-sandwich structure and is found in arrestin and related proteins. (ebi.ac.uk)
- Arrestins (abbreviated Arr) are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. (wikipedia.org)
- In addition to GPCRs, arrestins bind to other classes of cell surface receptors and a variety of other signaling proteins. (wikipedia.org)
- Arrestins block GPCR coupling to G proteins in two ways. (wikipedia.org)
- First characterized as blocking signal transduction by preventing interaction between receptor cytoplasmic domains and heterotrimeric G proteins, arrestins are now known to participate in endocytosis and signaling of 7TM receptors, e.g., by linking them to the endocytic internalization machinery ( 1 , 2 ). (pnas.org)
- Arrestins comprise a family of closely-related proteins. (ebi.ac.uk)
- show that β-arrestins, which limit signaling by GPCRs coupled to G proteins of the G s class, serve a very similar function in control of signaling by M1 muscarinic receptors. (sciencemag.org)
- In the cases of the manganese transporter Smf1 and the amino acid transporters Can1, Lyp1 and Mup1 it has been shown that ubiquitination is mediated by arrestin-like adaptor proteins that bind to Rsp5 and recognize specific transporters. (nih.gov)
- The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins 1 . (nature.com)
- These results reveal, at high resolution, a receptor-interacting interface on β-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins. (nature.com)
- For example he counts the accessory proteins arrestin and retinoid binding protein, but these can be completely absent in vertebrates with either no effect or mild night blindness eg. (wordnik.com)
- Arrestins constitute a superfamily of regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors. (nih.gov)
- Arrestins are regulatory proteins that down-regulate phosphorylated G-protein coupled receptors (GPCRs). (springer.com)
- βarrestins have an analogous function to rod arrestin in the termination of GPCR signaling by sterically inhibiting the coupling of phosphorylated receptors to their respective G proteins. (springer.com)
- The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). (abcam.com)
- Phosphorylated receptors recruit multifunctional adaptor proteins β-arrestins which sterically hinder further G protein coupling to the receptor and in turn lead to receptor desensitization. (nih.gov)
- Note that the majority of β-arrestin interaction partners are distributed in the cytoplasm but a significant fraction are nuclear proteins highlighting the potential nuclear roles of β-arrestins. (nih.gov)
- The functional distribution of β-arrestin binding proteins highlights their major roles in cellular signaling, cellular organization and nucleic acid binding. (nih.gov)
- Beta Arrestin 1 is a member of a family of proteins widely expressed but especially abundant in the central nervous system. (thermofisher.com)
- Additionally we are shipping Arrestin 3 Kits (40) and Arrestin 3 Proteins (8) and many more products for this protein. (antibodies-online.com)
- G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. (osti.gov)
- Arrestins bind a host of catalytically active proteins and serve as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into the receptor-arrestin complex. (aspetjournals.org)
- There are 9903 Arrestin_C domains in 9566 proteins in SMART's nrdb database. (embl.de)
- Taxonomic distribution of proteins containing Arrestin_C domain. (embl.de)
- The complete taxonomic breakdown of all proteins with Arrestin_C domain is also avaliable . (embl.de)
- Click on the protein counts, or double click on taxonomic names to display all proteins containing Arrestin_C domain in the selected taxonomic class. (embl.de)
- β-Arrestin 1 and 2 are highly expressed proteins involved in the desensitization of G protein-coupled receptor signaling which also regulate a variety of intracellular signaling pathways. (frontiersin.org)
- Arrestins are a family of auxiliary proteins associated with GPCRs that consist of four members: visual arrestin (arrestin 1), cone arrestin (arrestin 4), β-arrestin 1 (arrestin 2), and β-arrestin 2 (arrestin 3) ( Patwari and Lee, 2012 ). (frontiersin.org)
- Activated receptors are subsequently phosphorylated in complex patterns on intracellular domains by serine/threonine G protein-coupled receptor kinases (GRKs), which reduce receptor affinity for G proteins and increase receptor affinity for arrestins ( 7 - 10 ). (pubmedcentralcanada.ca)
- Furthermore, the discovery of biased GPCR ligands and the findings that distinct G-proteins versus β-arrestin signaling preferences may offer therapeutic advantages over conventional ligands imply that a screening campaign should be designed to focus on the most disease relevant pathways (7-10). (discoverx.com)
- To understand the role of arrestin in melanopsin function, we investigated the interaction mechanism of these two proteins. (arvojournals.org)
- Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. (pubmedcentralcanada.ca)
- G protein-coupled receptors are well recognized as being able to activate several signaling pathways through the activation of different G proteins as well as other signaling proteins such as β-arrestins. (frontiersin.org)
- GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. (diabetesjournals.org)
- β‑arrestins are a family of adaptor proteins that regulate the signaling and trafficking of various G protein‑coupled receptors (GPCRs). (spandidos-publications.com)
- Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. (biologists.org)
- The Dictyostelium discoideum genome encodes six arrestin-related proteins, harboring additional modules besides the arrestin domain. (biologists.org)
- Using fluorescently tagged proteins combined with resonance energy transfer and image cross-correlation spectroscopy approaches, we show in live cells that β2-adaptin phosphorylation is an important regulatory process for the dissociation of β-arrestin-AP-2 complexes in CCPs. (biologists.org)
- Arrestin proteins then bind to the phosphorylated receptor initializing clathrin-mediated internalization. (ahajournals.org)
- One potential nexus for GPCR signaling crosstalk are the multifunctional scaffold proteins known as arrestins. (ahajournals.org)
- Arrestins not only scaffold proteins for the activation of different MAPK families under single receptor activation, but also mediate transactivation of epidermal growth factor receptor signaling pathways 2,6 and activation of many other non-GPCR signaling cascades. (ahajournals.org)
- 7 In the case of GPCR-induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activation, both G proteins and arrestins are capable of mediating ERK activation via independent mechanisms, with each pathway leading to unique spatiotemporal consequences. (ahajournals.org)
- The classical visual and β-arrestins belong to a larger family of proteins that likely share structural similarity. (semanticscholar.org)
- Humans have an additional six related proteins sometimes termed the α-arrestins, whose functions are now emerging. (semanticscholar.org)
- Arrestins were initially named on the basis of their ability to turn-off the coupling of G protein-coupled receptors (GPCRs) to G proteins and thereby inhibit G protein-dependent GPCR signaling. (elifesciences.org)
- β‐arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven‐transmembrane receptor trafficking and signalling. (embopress.org)
- Other proteins with predicted 'arrestin‐like' structural domains but lacking sequence homology have been indicated to function like β‐arrestin in receptor regulation. (embopress.org)
- The arrestin‐domain‐containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized β 2 AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of β‐arrestin2. (embopress.org)
- Mammalian cells also express arrestin‐domain‐containing proteins (ARRDC 1-5 and the thioredoxin‐interacting protein TXNIP), which have predicted structural similarities with arrestins but lack sequence homology [ 4 , 5 , 6 , 7 ]. (embopress.org)
- In yeast, a small family of arrestin‐domain‐containing proteins with PPXY motifs function as arrestin‐related trafficking adaptors for the yeast HECT domain E3 ligase Rsp5, which regulates ubiquitination and trafficking of plasma membrane amino‐acid transporters [ 16 ]. (embopress.org)
- It has been reported that β-arrestins interact with a number of binding partners including trafficking proteins, cytosolic kinases, cytoskeletal proteins, and non-receptor tyrosine kinase. (escholarship.org)
Receptors41
- This inactivation is achieved, in part, by the binding of a soluble protein, arrestin, which uncouples the receptor from the downstream G protein after the receptors are phosphorylated by G protein-coupled receptor kinases. (ebi.ac.uk)
- In addition to the inactivation of G protein-coupled receptors, arrestins have also been implicated in the endocytosis of receptors and cross talk with other signalling pathways. (ebi.ac.uk)
- Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers. (wikipedia.org)
- Arrestin binding to the receptor blocks further G protein-mediated signaling and targets receptors for internalization, and redirects signaling to alternative G protein-independent pathways, such as β-arrestin signaling. (wikipedia.org)
- Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. (pnas.org)
- Of the four known mammalian arrestins, visual and cone arrestins are expressed in photoreceptors, regulating rhodopsin and cone opsins, respectively, whereas ubiquitously expressed β-arrestins 1 and 2 regulate many 7TM receptors. (pnas.org)
- Although fungal 7TM receptors have been characterized in fungi (e.g., ref. 5 ), experimentally documented arrestins have only been identified in metazoa. (pnas.org)
- Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals, as well as having signalling roles in their own right. (wikipedia.org)
- Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. (wikipedia.org)
- C. D. Nelson, S. J. Perry, D. S. Regier, S. M. Prescott, M. K. Topham, R. J. Lefkowitz, Targeting of diacylglycerol degradation to M1 muscarinic receptors by β-arrestins. (sciencemag.org)
- Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors. (nih.gov)
- Arrestins activated by interaction with phosphorylated receptors can also mediate G-protein-independent signalling by serving as adaptors to link receptors to numerous signalling pathways 4 . (nature.com)
- Receptor bound β-arrestins also recruit several components of clathrin dependent internalization machinery to the activated receptors and subsequently promote receptor endocytosis via clathrin coated pits. (nih.gov)
- Producer) Discusses the diversity of roles played by the beta-arrestins in regulating the function and trafficking of heptahelical (G protein-coupled) receptors. (worldcat.org)
- Non-visual arrestins were initially appreciated for the roles they play in the negative regulation of G protein-coupled receptors through the processes of desensitisation and endocytosis. (biomedsearch.com)
- The arrestins are also now known as protein scaffolding platforms that act downstream of multiple types of receptors, ensuring relevant transmission of information for an appropriate cellular response. (biomedsearch.com)
- Serving as an adaptor or scaffold molecule, beta Arrestin 1 is essential for mitogenic signaling and mediates agonist-dependent desensitization and internalization of Gprotein-coupled receptors (GPCRs, e.g., beta 2-adrenergic receptor). (thermofisher.com)
- Beta Arrestin 1 in the cytosol is phosphorylated by ERK1 and 2 on serine412 in a negative feedback mechanism and binds to the phosphorylated receptors at the plasma membrane. (thermofisher.com)
- β-Arrestins are ubiquitously expressed and function in the activation of GPCRs, desensitization of most 7-transmembrane receptors, and regulation of other signaling molecules such as protein kinases. (discoverx.com)
- Signaltermination is achieved by the action of the arrestins, which bind toactivated, phosphorylated G protein-coupled receptors. (embl.de)
- In this model, based primarily on studies of the β2-adrenergic receptor (β2-AR), adaptor protein (AP)-2 and clathrin bind the carboxy terminus of arrestin ( 14 ), translocating receptors to clathrin-coated pits for internalization. (pubmedcentralcanada.ca)
- β-Arrestins are ubiquitously expressed in all cell types, and function in the desensitization of G- protein coupled receptors (GPCRs), the control of GPCR intracellular trafficking, and the activation of GPCRs to multiple signaling pathways (1-4). (discoverx.com)
- In summary, we provide experimental evidence of biased agonism for FPR2 and our data disclose critical roles of β-arrestin in neutrophil chemotaxis and reactivation of desensitized receptors. (ovid.com)
- G protein-coupled receptor kinases (GRKs) were initially identified as serine/threonine kinases that participate, together with β-arrestins, in the regulation of multiple G protein-coupled receptors (GPCRs). (diabetesjournals.org)
- Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A receptors was prevented in cells stably transfected with either CB2 or β-Arrestin 2 shRNA lentiviral particles. (ku.edu)
- Our results indicate that cannabinoid agonists might upregulate 5-HT2A receptors by a mechanism that requires CB2 receptors and β-Arrestin 2 in cells that express both CB2 and 5-HT2A receptors. (ku.edu)
- β-Arrestins regulate G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors through receptor desensitization while also acting as signaling scaffolds to facilitate numerous effector pathways. (sciencemag.org)
- β-arrestin (βarr)-2 is a multifunctional scaffolding protein that binds G-protein-coupled receptors such as AngII type 1a and regulates numerous signaling pathways and pathophysiological processes. (ahajournals.org)
- Recently, a requirement for β-arrestin-mediated endocytosis in the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by several G protein-coupled receptors (GPCRs) has been proposed. (rupress.org)
- β-arrestins are known to act as endocytic adaptors by recruiting the clathrin adaptor protein 2 (AP-2) complex to G-protein-coupled receptors (GPCRs), linking them to clathrin-coated pits (CCPs) for internalization. (biologists.org)
- Beyond their classical function, β-arrestins act as signaling adaptors linking receptors to multiple downstream effectors. (biologists.org)
- β-Arrestin-1 mediates agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCRs) and is also essential for GPCR mitogenic signaling. (asm.org)
- Adrenergic receptors on cardiac fibroblasts were manipulated to examine the role of arrestin in the spatiotemporal regulation of extracellular signal-regulated kinase (ERK)1/2 MAPK signaling. (ahajournals.org)
- In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. (elifesciences.org)
- Here, we show that activation of serotonin 5-HT 2C receptors, which engage Erk1/2 pathway via a β-arrestin-dependent mechanism, promotes MEK-dependent β-arrestin2 phosphorylation at Thr 383 , a necessary step for Erk recruitment to the receptor/β-arrestin complex and Erk activation. (elifesciences.org)
- Likewise, Thr 383 phosphorylation is involved in β-arrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as β 2 -adrenergic, FSH and CXCR4 receptors, but does not affect the β-arrestin-independent Erk1/2 activation by 5-HT 4 receptor. (elifesciences.org)
- Activated G q protein-coupled receptors (G q PCRs) can be desensitized by phosphorylation and β-arrestin binding. (rupress.org)
- Thus, PAR2 may continuously regain its activity via dephosphorylation when there is insufficient β-arrestin to trap phosphorylated receptors. (rupress.org)
- Ligand binding to β 2 -adrenergic receptors promotes homologous phosphorylation by GRK, which enhances binding of β-arrestin to the phosphorylated receptor. (rupress.org)
- β-arrestins, originally discovered in the context of G protein-coupled receptor (GPCR) desensitization and internalization, also function in signaling of these receptors independently of G protein coupling. (escholarship.org)
- Barbadin blocks agonist-promoted endocytosis of the prototypical β2-adrenergic, V2-vasopressin and angiotensin-II type-1 receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. (axonmedchem.com)
Beta-arrestins7
- The arrestin superfamily includes visual arrestins, beta-arrestins (βarrestins) and insect chemosensory arrestins. (springer.com)
- New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization, J Biol Chem 273 (30), 18677-18680 (1998). (springer.com)
- Lefkowitz, Shenoy: Transduction of receptor signals by beta-arrestins. (antibodies-online.com)
- Expression of two beta-arrestins - Arrb1 and Arrb2 in ipRGCs was analyzed by single cell qPCR. (arvojournals.org)
- C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways. (sigmaaldrich.com)
- Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination. (semanticscholar.org)
- METHODS/RESULTS: 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 beta-arrestins. (duke.edu)
GPCRs17
- It was first named β-arrestin simply because between two GPCRs available in purified form at the time, rhodopsin and β2-adrenergic receptor, it showed preference for the latter. (wikipedia.org)
- The second non-visual arrestin cloned was first termed β-arrestin-2 (retroactively changing the name of β-arrestin into β-arrestin-1), even though by that time it was clear that non-visual arrestins interact with hundreds of different GPCRs, not just with β2-adrenergic receptor. (wikipedia.org)
- Despite their central role in regulation and signalling of GPCRs, a structural understanding of β-arrestin activation and interaction with GPCRs is still lacking. (nature.com)
- GPCRs and Arrestins in Airways: Implications for Asthma. (biomedsearch.com)
- Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. (osti.gov)
- For GPCRs, ligand-induced β-arrestin recruitment activates signaling cascades independent of G-protein signaling to provide a non-amplified signal which is ideal for antagonist mode screening, studying ligand pharmacologies, and deorphanizing GPCRs. (discoverx.com)
- Complex formation between phosphorylated GPCRs, arrestins and an ever-increasing number of effector molecules is known to regulate cellular function. (pubmedcentralcanada.ca)
- As many GPCRs are found to recruit β-arrestin, the β-arrestin recruitment assay has found important use in drug discovery, especially in the discovery of ligands for orphan GPCRs and in situations where the second messenger signaling is unknown (5,6). (discoverx.com)
- PathHunter β-Arrestin cell lines are stable clonal cell lines that expedite drug discovery and development by providing robust response to over 90% of all known G-protein coupled receptor (GPCRs), with accurate pharmacology. (discoverx.com)
- This assay measures an essential pathway in GPCR activation, i.e. β-arrestin recruitment to activated GPCRs, enabling scientists to screen for and profile functional agonists and inhibitors of GPCRs. (discoverx.com)
- It has been demonstrated that β‑arrestins serve roles in various physiological and pathological processes and exhibit a similar function to GPCRs. (spandidos-publications.com)
- Although, β-arrestin can assume both roles of signaling and endocytic adaptor for many GPCRs, it is still largely unknown whether the recruitment of signaling molecules to β-arrestin impacts its endocytic function. (biologists.org)
- Because arrestins preferentially bind to some, but not all, GPCRs in a ligand-dependent manner, we envision that arrestins may play a role in GPCR crosstalk by coordinating MAPK activation in distinct subcellular compartments. (ahajournals.org)
- Collectively, these data show that β-arrestin2 phosphorylation at Thr 383 underlies β-arrestin-dependent Erk1/2 activation by GPCRs. (elifesciences.org)
- Typically, most GPCRs induce temporally distinct and spatially segregated G protein-dependent and β-arrestin-dependent activation of Erk: G protein-mediated Erk activation is rapid and transient, reaching a maximal level within a few minutes and is followed by translocation of activated Erk into the nucleus to promote gene transcription and cell proliferation. (elifesciences.org)
- These effects of β-arrestin knockdown on PIP 2 recovery were prevented when serine/threonine phosphatases that dephosphorylate GPCRs were inhibited. (rupress.org)
- Upon activation, most mammalian GPCRs are phosphorylated in the C-terminal region by G-protein receptor kinases, which serve to recruit arrestin. (arvojournals.org)
GPCR33
- 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. (jci.org)
- In conclusion, this structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology. (osti.gov)
- Create your own GPCR β-arrestin cell-based assays to evaluate ligand-induced β-arrestin recruitment to any GPCR in any cell type. (discoverx.com)
- Using the enzyme fragment complementation technology, simply infect your target cells with the PathHunter β-Arrestin Retroparticles, transfect the cells with a GPCR plasmid, and perform a PathHunter GPCR β-arrestin assay with your ligand of interest. (discoverx.com)
- PathHunter GPCR β-Arrestin assays take advantage of DiscoverX's proprietary Enzyme Fragment Complementation technology. (discoverx.com)
- The GPCR is fused in frame with a small enzyme donor fragment ProLink™ (PK) and co-expressed in cells stably expressing a fusion protein of β-arrestin and the larger, N-terminal deletion mutant of β-galactosidase (called enzyme acceptor or EA). (discoverx.com)
- Activation of the GPCR stimulates binding of β-arrestin to the PK-tagged GPCR and forces complementation of the two enzyme fragments, resulting in the formation of an active β-galactosidase enzyme. (discoverx.com)
- 2009) uncovers a role for beta-arrestin, previously known to control GPCR desensitization, in insulin signaling. (garvan.org.au)
- In this study, we show that the interaction of GPCR-bound arrestin with Adaptor Protein 2 (AP-2) is a critical anti-apoptotic event. (pubmedcentralcanada.ca)
- In addition, AP-2 associates with the receptor-arrestin complex in perinuclear endosomes and is required for proper post-endocytic GPCR trafficking. (pubmedcentralcanada.ca)
- We propose a model in which the abnormal accumulation of internalized GPCR-arrestin complexes in recycling endosomes, resulting from defective arrestin-AP-2 interactions, leads to the specific initiation of aberrant signaling pathways and apoptosis. (pubmedcentralcanada.ca)
- Tools & Resources / Publications & References / Publications / Measurement of β-Arrestin Recruitment for GPCR Targets. (discoverx.com)
- Therefore, β-arrestin-mediated signaling constitutes an important part of GPCR signaling in addition to G protein-mediated signaling. (discoverx.com)
- There are four major in vitro assay technologies available on the market that are capable of measuring ligand-induced β-arrestin recruitment: PathHunter β-arrestin Assay (DiscoverX) (11), Tango GPCR Assay (Thermo Fisher Scientific) (12), LinkLight GPCR/ β-arrestin Signaling Pathway Assay (BioInvenu) (13), and Transfluor Assay (Molecular Devices) (14). (discoverx.com)
- The PathHunter β-arrestin Assay, Tango GPCR Assay System and LinkLight GPCR/ β-arrestin Signaling Pathway Assays are homogenous, high throughput assays while the Transfluor Assay is a fluorescence image-based assay. (discoverx.com)
- All four assays involve the expression of the β-arrestin as a fusion protein with another protein or fragment, while the PathHunter, Tango and LinkLight assays require fusion of the GPCR to another peptide or protein moiety as well. (discoverx.com)
- β-arrestins regulate G protein-coupled receptor (GPCR) function and also mediate GPCR-independent signaling. (ahajournals.org)
- MMP-2 expression was upregulated 1.5-fold in failing CF. In conclusion, our results suggest that β-arrestins play an important role in the regulation of collagen synthesis and degradation by CF. This occurs through GPCR (β-AR/cAMP) and GPCR-independent (TGF-β/ERK) mechanisms. (ahajournals.org)
- Consequently, interesting conclusions have been reported regarding GPCR-G protein coupling, interaction between G protein subunits, and GPCR-arrestin association in terms of structure, pharmacology, and kinetic of activation/deactivation. (frontiersin.org)
- GRK2-mediated phosphorylated GPCR promotes the binding of β-arrestin 2, which is reportedly ubiquitously expressed, and then mediates various signal-transduction pathways such as Akt ( 12 ). (diabetesjournals.org)
- 13 ) reported that insulin stimulates the formation of a new β-arrestin 2 signal complex in which β-arrestin 2 acts as a scaffold for translocation of Akt to IR, even though IR is not a GPCR. (diabetesjournals.org)
- DiscoveRx has announced the release of the PathHunter™ Flash Detection Kit to enable ß-arrestin recruitment by a GPCR in 30 seconds, permitting screens of up to 1,000,000 compounds in 48 hours. (technologynetworks.com)
- A ligand-activated, GPCR-arrestin interaction combines two ß-galactosidase fragments, enabling rapid chemiluminescent detection in a homogeneous format. (technologynetworks.com)
- β-Arrestin GPCR cells are engineered to co-the ProLink (PK) tagged GPCR and the Enzyme Acceptor (EA) tagged β-Arrestin. (creativebiomart.net)
- Activation of the GPCR-PK induces β-Arrestin-EA recruitment, forcing complementation of the two β-galactosidase enzyme fragments (EA and PK). (creativebiomart.net)
- We have previously shown that stimulation of the angiotensin II (Ang II) type 1 receptor (AGTR1, hereafter referred to as AT1R), a member of the GPCR family, promotes the formation of a complex between β-arrestin, the kinase Src and AP-2. (biologists.org)
- β-arrestins are adaptor molecules that have been first described in playing a role in G-protein-coupled receptor (GPCR) desensitization. (biologists.org)
- iii) Finally, these results describe a novel mechanism for heterologous desensitization, whereby insulin treatment can impair GPCR signaling, and highlight the importance of β-arrestin-1 as a target molecule for this desensitization mechanism. (asm.org)
- We show a general mechanism in which arrestin activation by one GPCR is capable of regulating signaling originating from another GPCR. (ahajournals.org)
- The present study explores the mechanisms of GR internalization and the role of PKCα, GPCR kinases (GRKs) and β-arrestins therein. (ovid.com)
- This item specifically recognises human beta arrestin-2 (ARRB2), a scaffolding protein and member of the arrestin family, highly expressed in the central nervous system, which plays a role in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling, through receptor desensitization and internalization. (mybiosource.com)
- Arrestin-binding often competes with G-protein for GPCR interaction and constitutes the mechanism of deactivation. (arvojournals.org)
- A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. (axonmedchem.com)
Phosphorylation21
- GRK phosphorylation specifically prepares the activated receptor for arrestin binding. (wikipedia.org)
- By using mutants of the β 1 AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against β-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires β 1 AR phosphorylation at consensus G protein-coupled receptor kinase sites and β-arrestin recruitment to the ligand-occupied receptor. (pnas.org)
- Turning off the G protein signal by a process known as desensitization occurs through G protein-coupled receptor kinase (GRK) phosphorylation of the 7TMR, and subsequent binding of β-arrestin ( 1 , 2 ). (pnas.org)
- B ) Insulin-induced phosphorylation of AKT and GSK3α/β remains unaffected by the lack of β-arrestin 2 in hepatocytes. (jci.org)
- Recent global analyses of β-arrestin interactions and β-arrestin-dependent phosphorylation events have uncovered several previously unanticipated roles of β-arrestins in a range of cellular signaling events. (nih.gov)
- (b) GRK-mediated phosphorylation and β-arrestin-mediated desensitization of 7TMRs. (nih.gov)
- The global scope of the β-arrestin interactome and β-arrestin dependent phosphorylation events. (nih.gov)
- Krishnamurthy, Galet, Ascoli: The association of arrestin-3 with the follitropin receptor depends on receptor activation and phosphorylation. (antibodies-online.com)
- Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. (harvard.edu)
- β-arrestin 1 knockdown led to a significant decline in TGF-β-stimulated collagen synthesis in normal and failing CF. This is likely mediated by decreased ERK 1/2 phosphorylation and activation which resulted from β-arrestin 1 knockdown. (ahajournals.org)
- Although visual arrestin has been shown to quench the catalytic activity of photoexcited, phosphorylated rhodopsin in a reconstituted system, its role in the intact rod cell remains unclear because phosphorylation alone reduces the catalytic activity of rhodopsin. (semanticscholar.org)
- Duration and amplitude of the light-induced cGMP hydrolysis in vertebrate photoreceptors are regulated by multiple phosphorylation of rhodopsin and by arrestin binding. (semanticscholar.org)
- Here, we report that formation of such a complex is involved in the AT1R-mediated tyrosine phosphorylation of β2-adaptin, the subunit of AP-2 involved in binding β-arrestin. (biologists.org)
- We identify a crucial tyrosine residue in the ear domain of β2-adaptin and show in vitro that the phosphorylation of this site regulates the interaction between β-arrestin and β2-adaptin. (biologists.org)
- We also found a marked decrease in the association of β-arrestin-1 with the IGF-IR and a 55% inhibition of IGF-I-stimulated MAP kinase phosphorylation. (asm.org)
- In insulin-treated, β-arrestin-1-downregulated cells, there was complete inhibition of lysophosphatidic acid (LPA) or isoproterenol (ISO)-stimulated MAP kinase phosphorylation. (asm.org)
- Ectopic expression of wild-type β-arrestin-1 in insulin-treated cells in which endogenous β-arrestin-1 had been downregulated rescued IGF-I- and LPA-stimulated MAP kinase phosphorylation. (asm.org)
- Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. (figshare.com)
- This phosphorylation barcode is translated into specific β-arrestin conformations that dictate selective signaling and the nature of β-arrestin intracellular functions. (elifesciences.org)
- Another mechanism that might underlie β-arrestin dependency of receptor-operated signaling is the phosphorylation of β-arrestins themselves. (elifesciences.org)
- Simulations supported the conclusions that phosphorylation of PAR2 by protein kinases initiates receptor desensitization and that recruited β-arrestin traps the phosphorylated state of the receptor, protecting it from phosphatases. (rupress.org)
Interaction13
- The strength of arrestin-receptor interaction plays a role in this choice: tighter complexes tend to increase the probability of receptor degradation (Class B), whereas more transient complexes favor recycling (Class A), although this "rule" is far from absolute. (wikipedia.org)
- Substitution in PalF of a highly conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction and pH signaling in vivo . (pnas.org)
- What's more, our results suggested that the interaction between β-arrestin 2 and Zbtb46 might negatively regulate DC migration. (jimmunol.org)
- Using RNA sequencing, we indicated that genes CD74, NR4A1, and ZFP36 might be the target genes regulated by the interaction between β-arrestin 2 and Zbtb46. (jimmunol.org)
- HEK-293 cells were transiently transfected with full-length or C-terminal truncated melanopsin and arrestin, and its interaction with arrestin was investigated by co-immunoprecipitation assay. (arvojournals.org)
- Upon interaction with FPR2 expressed by neutrophils both F2Pal10 and WKYMVM activated the PLC-PIP2-Ca2+ signaling pathway and the superoxide-generating NADPH-oxidase, but only WKYMVM activated the receptor to recruit β-arrestin. (ovid.com)
- In contrast, the antibody did not block the interaction of the 399myc or 99myc100 arrestins with the receptor and was found specifically in the arrestin-rhodopsin pellets for light-reactions. (arvojournals.org)
- Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian β-arrestin family, which is predicted to share similar tertiary structure with visual-/β-arrestins and also contains C-terminal PPxY motifs that mediate interaction with E3 ubiquitin ligases. (jefferson.edu)
- PAR4SFT supported only 8.74% of PAR4 P2Y12 interaction, abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation. (aspetjournals.org)
- Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. (figshare.com)
- non‐visual arrestin 2 and 3) contain a characteristic α‐helix in the N‐terminal domain and a polar core that keeps the molecule constrained in a basal conformation, which is disrupted on arrestin-receptor interaction [ 8 , 9 ]. (embopress.org)
- We hypothesized that the ability of β-arrestins to scaffold and prolong MAPK signaling at the membrane, is dependent upon precise molecular interactions that are facilitated by interaction of β-arrestins with PAR-2. (escholarship.org)
- Selective β-arrestin/β2-adaptin interaction inhibitor (IC50 values of 19.1 and 15.6 μM for β-arrestin1 and β-arrestin2, respectively). (axonmedchem.com)
Antibody11
- To capture this active conformation, we used a conformationally selective synthetic antibody fragment (Fab30) that recognizes the phosphopeptide-activated state of β-arrestin-1. (nature.com)
- The following antibody was used in this experiment: S-arrestin Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA1-731, RRID AB_2183220. (thermofisher.com)
- By Western blot this antibody detects an ~57 kDa protein representing recombinant bovine and sheep visual arrestin. (thermofisher.com)
- The following product was used in this experiment: beta Arrestin 1 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-35089, RRID AB_2552399. (thermofisher.com)
- There are currently no images for S-arrestin Antibody (NBP2-25161B). (novusbio.com)
- The binding of light-activated, phosphorylated rhodopsin to the 162myc163 or 72myc73 arrestins in solution was completely inhibited in the presence of less than 2-fold molar excess anti-myc antibody relative to arrestin. (arvojournals.org)
- Arrestin antibody LS-C141017 is a DY550-conjugated mouse monoclonal antibody to Arrestin (SAG) from pig. (lsbio.com)
- RAW264.7 cells were subjected to SDS PAGE followed by western blot with 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:2000 incubated at room temperature for 1.5 hours. (ptglab.com)
- Immunohistochemical analysis of paraffin-embedded human tonsil tissue slide using 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:200 (under 10x lens). (ptglab.com)
- Immunohistochemical analysis of paraffin-embedded human tonsil tissue slide using 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:200 (under 40x lens). (ptglab.com)
- This antibody is specific for arrestin protein. (mybiosource.com)
Regulate7
- β-Arrestin 1 and 2 (Barr1 and Barr2, respectively) are intracellular signaling molecules that regulate many important metabolic functions. (jci.org)
- Although many of these arrestin-bound effectors serve to modulate G protein signaling, degrading second messengers and regulating endocytosis and trafficking, other signals seem to extend beyond the receptor-arrestin complex to regulate such processes as protein translation and gene transcription. (aspetjournals.org)
- In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. (diabetesjournals.org)
- β‑arrestins regulate cell proliferation, promote cell invasion and migration, transmit anti‑apoptotic survival signals and affect other characteristics of tumors, including tumor growth rate, angiogenesis, drug resistance, invasion and metastatic potential. (spandidos-publications.com)
- Here we show that PAR4 and P2Y12 directly interact to co-regulate arrestin-2 signaling following PAR4 activation. (aspetjournals.org)
- We hypothesize that β-arrestins regulate oxidative stress in a Nox4-dependent manner and increase fibrosis in HF. (biologists.org)
- An expanded family of arrestins regulate metabolism. (semanticscholar.org)
Photoreceptors7
- Insects have arr1 and arr2, originally termed "visual arrestins" because they are expressed in photoreceptors, and one non-visual subtype (kurtz in Drosophila). (wikipedia.org)
- In mammals, arrestin-1 and arrestin-4 are largely confined to photoreceptors, whereas arrestin-2 and arrestin-3 are ubiquitous. (wikipedia.org)
- Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. (wordnik.com)
- Two members of visual arrestins have been identified in vertebrate photoreceptors: rod arrestin (also known as S-antigen or Arrestin 1) and cone arrestin (X-arrestin or Arresting. (springer.com)
- In vertebrate rod photoreceptors, rod arrestin quenches the light-induced phototransduction cascade by binding preferentially to the light-activated, phosphorylated rhodopsin. (springer.com)
- Mouse cone photoreceptors express two visual arrestins, Arr1 and Arr4 (Carr). (pubmedcentralcanada.ca)
- Arrestin competition influences the kinetics and variability of the single-photon responses of mammalian rod photoreceptors. (semanticscholar.org)
Endocytosis6
- Importantly, both ubiquitination and dephosphorylation of β-arrestins appear essential to agonist-dependent receptor endocytosis ( 3 , 4 ). (pnas.org)
- We have tested this model by removing all the arrestins and examining the requirements for endocytosis of four more transporters, Itr1 (inositol), Hxt6 (glucose), Fur4 (uracil) and Tat2 (tryptophan). (nih.gov)
- Role of beta-arrestin 1-dependent targeting of c-SRC in receptor endocytosis, J Biol Chem 275 (15), 11312-11319 (2000). (springer.com)
- (c) Novel roles of β-arrestins as endocytosis adaptors, E3 ubiquitin ligase adaptors and the new paradigm of β-arrestin dependent signaling downstream of 7TMRs. (nih.gov)
- In addition, insulin-like growth factor I receptor (IGF-IR) endocytosis is facilitated by β-arrestin-1, and internalization is necessary for IGF-I-stimulated mitogen-activated protein (MAP) kinase activation. (asm.org)
- β‐arrestins 1 and 2 mediate clathrin‐dependent endocytosis of the β 2 AR [ 18 , 19 , 20 ]. (embopress.org)
Internalization7
- Second, arrestin links the receptor to elements of the internalization machinery, clathrin and clathrin adaptor AP2, which promotes receptor internalization via coated pits and subsequent transport to internal compartments, called endosomes. (wikipedia.org)
- G protein signaling is terminated, in large part, by arrestin binding, which uncouples the receptor and G protein and targets the receptor for internalization. (aspetjournals.org)
- Previous studies have demonstrated that, although N -formyl peptide receptor (FPR) internalization occurs in the absence of arrestins, FPR recycling is arrestin-dependent. (pubmedcentralcanada.ca)
- Arrestin binding sterically blocks receptor-G protein interactions, thereby terminating G protein signaling, while simultaneously providing a scaffold to coordinate the recruitment of internalization machinery, leading to receptor sequestration ( 11 - 13 ). (pubmedcentralcanada.ca)
- Further, the inability to recruit β-arrestin was found to be associated with a reduced rate of receptor internalization and impaired chemotaxis in neutrophils. (ovid.com)
- Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin. (semanticscholar.org)
- Furthermore, both β-arrestin1 and β-arrestin2 colocalized with GR and with Cav-1, suggesting the possible involvement of these arrestins in GR internalization. (ovid.com)
GRKs2
- Multifaceted roles of β-arrestins and GRKs in 7TMR signaling and regulation. (nih.gov)
- G protein subunits, RGS, arrestins, GRKs …) to the activated receptor or conformational changes within their preassembled or newly formed complexes ( 6 - 10 ). (frontiersin.org)
Role of arrestin2
- The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin in Xenopus laevis, the principle amphibian biological model system. (nih.gov)
- To understand the regulation of melanopsin function, here we investigated the role of arrestin. (arvojournals.org)
Bind2
- Please note that the different binding partners of β-arrestins shown in the figure probably do not bind β-arrestins simultaneously. (nih.gov)
- We have proved that β-arrestin-1 binds to the regulatory domain of c-Raf where Ras was indentified to bind. (escholarship.org)
Visual arrestins1
- Recordings from Arr1 −/− , Arr4 −/− double-knockout mice establish a requirement for at least one of the two visual arrestins for normal cone opsin inactivation at all flash intensities. (pubmedcentralcanada.ca)
Rhodopsin13
- The binding region for phosphorylated light-activated rhodopsin is located at the N-terminal domain, as indicated by the docking of the photoreceptor to the three-dimensional structure of arrestin. (ebi.ac.uk)
- On the origins of arrestin and rhodopsin. (ebi.ac.uk)
- The systematic arrestin name (1-4) plus the most widely used aliases for each arrestin subtype are listed in bold below: Arrestin-1 was originally identified as the S-antigen (SAG) causing uveitis (autoimmune eye disease), then independently described as a 48 kDa protein that binds light-activated phosphorylated rhodopsin before it became clear that both are one and the same. (wikipedia.org)
- Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. (curehunter.com)
- Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. (osti.gov)
- Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. (osti.gov)
- Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. (osti.gov)
- These recordings also reveal low activity photoproducts of S- and M-opsins that are absent when Grk1 and an arrestin are co-expressed, but which decay 70-fold more rapidly than the comparable photoproducts of rhodopsin in rods. (pubmedcentralcanada.ca)
- Visual arrestin inactivates the phototransduction cascade by specifically binding to light-activated, phosphorylated rhodopsin. (arvojournals.org)
- Recombinant arrestins containing the ten amino acid c-myc tag (EQKLISEEDL) at different positions were generated in yeast, purified on affinity columns and tested for binding to rhodopsin in centrifugation assays. (arvojournals.org)
- When the myc tag was placed on the C-terminus after amino acid 399, between amino acids 99-100 or 162-163 in arrestin, binding to rhodopsin was found to be very similar to wild-type. (arvojournals.org)
- The results indicate that an interactive surface for rhodopsin is located on or near the concave region of the N-domain of arrestin. (arvojournals.org)
- To examine the molecular processes that lead to light-induced retinal degeneration, mutant mice deficient in arrestin and rhodopsin kinase were raised in the dark and then subjected to relatively low doses of white light. (caltech.edu)
Pathways5
- Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, β-arrestin-dependent fashion. (pnas.org)
- Arrestins as regulatory hubs in cancer signalling pathways. (biomedsearch.com)
- Understanding the signaling roles of arrestins may foster the development of pathway-selective drugs that exploit these pathways for therapeutic benefit. (aspetjournals.org)
- β‑arrestins serve primary roles in cancer invasion and metastasis via various signaling pathways. (spandidos-publications.com)
- The present review assessed the function and mechanism of β‑arrestins in cancer invasion and metastasis via multiple signaling pathways, including mitogen‑activated protein kinase/extracellular signal regulated kinase, Wnt/β‑catenin, nuclear factor‑κB and phosphoinositide‑3 kinase/Akt. (spandidos-publications.com)
Gene9
- Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. (ebi.ac.uk)
- Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, after the chromosome where its gene resides. (wikipedia.org)
- In the HUGO database its gene is called arrestin-3. (wikipedia.org)
- Conserved positions of multiple introns in its gene and those of our arrestin subtypes suggest that they all evolved from this ancestral arrestin. (wikipedia.org)
- Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene. (wikipedia.org)
- The adaptive evolutionary relationship of Xenopus cone arrestin to the arrestin gene tree suggests high intrafamily homology and early gene duplication events. (nih.gov)
- Unlike lengthy reporter gene assays, PathHunter ß-arrestin assays are direct and hence minimize the opportunity for off-target effects. (technologynetworks.com)
- 8 Whereas G protein-dependent ERK translocates to the nucleus for gene transcription, arrestin-dependent ERK remains within the cytoplasm. (ahajournals.org)
- Diesel exhaust particles activate the matrix-metalloproteinase-1 gene in human bronchial epithelia in a beta-arrestin-dependent manner via activation of RAS. (duke.edu)
ARRB21
- On www.antibodies-online.com are 98 Arrestin, beta 2 (ARRB2) Antibodies from 23 different suppliers available. (antibodies-online.com)
Bovine3
- The crystal structure of bovine retinal arrestin comprises two domains of antiparallel beta-sheets connected through a hinge region and one short alpha-helix on the back of the amino-terminal fold [ PMID: 9495348 ]. (ebi.ac.uk)
- X-ray crystal structure of arrestin from bovine rod outer segments. (ebi.ac.uk)
- PA1-731 detects recombinant bovine and sheep visual arrestin. (thermofisher.com)
Assay5
- The β-arrestin recruitment assay followed by the second messenger (cAMP) assay were performed on the same cell line expressing human cholinergic muscarinic 2 (CHRM2) fused with PK. (discoverx.com)
- Only using the β-arrestin recruitment assay (left) revealed the possible true partial agonist pharmacology for oxo-M due to the non-amplified signal nature of the β-arrestin pathway compared to the amplified G-protein dependent pathway (right). (discoverx.com)
- In this aspect, the β-arrestin recruitment assay has added an important piece to the repertoire of assay tools in drug discovery. (discoverx.com)
- The principle behind this guideline can be applied to all the β-arrestin assay technologies. (discoverx.com)
- E ) A TUNEL assay revealed that apoptosis was attenuated when β-arrestin-2 was silenced. (aging-us.com)
Retinal S-antigen2
Recruitment7
- They direct the recruitment, activation, and scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, β-arrestins 1 and 2. (sciencemag.org)
- The functional consequences linked to a lack of β-arrestin recruitment were further explored, and we demonstrate that FPR2 desensitization occurred independent of β-arrestin. (ovid.com)
- Since β-arrestin recruitment occurs independent of G-protein coupling, these assays provide a direct, universal platform for measuring receptor activation. (discoverx.com)
- Our previous studies demonstrated that thrombin induces co-immunoprecipitation of PAR4 with P2Y12, together with arrestin recruitment to the complex. (aspetjournals.org)
- Further studies revealed that recruitment of arrestin3 to the β 2 -adrenergic receptor orchestrates the sequestration of Gq-coupled receptor-induced ERK to the cytosol through direct binding of ERK to arrestin. (ahajournals.org)
- Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. (figshare.com)
- Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. (figshare.com)
Molecular2
- In conjunction withbiochemical and mutagenesis data, we propose a molecular mechanism bywhich arrestin is activated for receptor binding. (embl.de)
- Although a number of recent studies reported that β-arrestins are required for ERK1/2 activation independently of G protein coupling, molecular mechanism of β-arrestin- mediated ERK1/2 activation via c-Raf has remained unclear. (escholarship.org)
Protein-coupled receptor kinase1
- A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). (harvard.edu)
Conformation6
- To determine whether β-adrenergic ligands that do not activate G protein signaling (i.e., β-blockers) can stabilize the β 1 AR in a signaling conformation, we screened 20 β-blockers for their ability to stimulate β-arrestin-mediated EGFR transactivation. (pnas.org)
- The structure of the β-arrestin-1-V2Rpp-Fab30 complex shows marked conformational differences in β-arrestin-1 compared to its inactive conformation. (nature.com)
- We describe herecrystallographic studies of visual arrestin in its basal conformation. (embl.de)
- 17. Is Signaling Specificity Encoded in Arrestin Conformation? (ellibs.com)
- β-arrestin (βarr) was recruited at a reduced level to CXCR3B relative to CXCR3A, which was also associated with differences in βarr2 conformation. (sigmaaldrich.com)
- In addition, a mysterious link in functional mechanism of β-arrestin-mediated ERK1/2 activation is how c-Raf relieves autoinhibition engendering a conformation change from a closed, inactive state to an open, active state, without small GTPase Ras, which is critical for c-Raf activation in the classical G protein dependent ERK activation. (escholarship.org)
Residues2
- A synthetic peptide corresponding to C terminal residues of Human Beta Arrestin 2 (UniProt: P32121). (abcam.com)
- The PA1-731 immunizing peptide corresponds to amino acid residues 2-18 from rat visual arrestin. (thermofisher.com)
Kinases1
- Altogether, our experimental and theoretical approaches demonstrate roles and dynamics of the protein kinases, β-arrestin, and PIP5K in the desensitization of PAR2. (rupress.org)
Superfamily1
- The arrestin superfamily: cone arrestins are a fourth family. (ebi.ac.uk)
Regulation3
- S-antigen, also identified as arrestin, is a protein involved in the regulation of phototransduction. (thermofisher.com)
- This response requires the calcium-dependent membrane-targeting C2 domain and the double SAM domain involved in AdcC oligomerization, revealing a mode of membrane targeting and regulation unique among members of the arrestin clan. (biologists.org)
- Surprisingly, several α-arrestins play prominent roles in the regulation of metabolism and obesity. (semanticscholar.org)
Kinase4
- W. E. Miller, S. Maudsley, S. Ahn, K. D. Khan, L. M. Luttrell, and R. J. Lefkowitz, beta-arrestin 1 interacts with the catalytic domain of the tyrosine kinase c-SRC. (springer.com)
- This insulin-induced decrease in β-arrestin-1 content was blocked by inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) and MEK with wortmannin and PD98059, respectively. (asm.org)
- ii) This downregulation of endogenous β-arrestin-1 is associated with decreased IGF-I-, LPA-, and ISO-mediated MAP kinase signaling, which can be rescued by ectopic expression of wild-type β-arrestin-1. (asm.org)
- Speculative thinking suggested a sequestration of phosphatidylinositol 4-phosphate 5 kinase (PIP5K) to the plasma membrane by β-arrestin to explain why knockdown of β-arrestin led to secondary depletion of PIP 2 . (rupress.org)
Plasma membrane2
- Arrestin-recruited Src then phosphorylates dynamin, which pinches off the plasma membrane invagination to form an endosome, whereupon arrestin dissociates from the receptor ( 15 ). (pubmedcentralcanada.ca)
- Downstream of protease-activated receptor-2 (PAR-2), β-arrestin scaffolds the components of the ERK cascade, Raf-1, MEK1, and ERK1/2 with the receptor at the plasma membrane, leading to activation of cytoplasmic/membrane ERK1/2 signaling independent of G-protein coupling. (escholarship.org)
Adaptors2
Desensitization4
- First, arrestin binding to the cytoplasmic face of the receptor occludes the binding site for heterotrimeric G-protein, preventing its activation (desensitization). (wikipedia.org)
- In vivo, the duality of arrestin function makes it difficult to dissociate the consequences of arrestin-dependent desensitization from those that might be ascribed to arrestin-mediated signaling. (aspetjournals.org)
- S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. (genetex.com)
- Knockdown of β-arrestin 1 and 2 using siRNA diminished the desensitization, slowing PIP 2 restoration significantly and even adding a delayed secondary phase of further PIP 2 depletion. (rupress.org)
Specificity1
- Interestingly, β-arrestin 2 knockdown did not have this effect, demonstrating specificity for regulating TGF-β-stimulated collagen synthesis. (ahajournals.org)
Mammalian2
- Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-dependent manner. (pnas.org)
- Control of rhodopsin's active lifetime by arrestin-1 expression in mammalian rods. (semanticscholar.org)
Ubiquitination1
- Here, we report that treatment of cells for 12 h with insulin (100 ng/ml) induces an ∼50% decrease in cellular β-arrestin-1 content due to ubiquitination of β-arrestin-1 and proteosome-mediated degradation. (asm.org)
Thioredoxin-interac2
- For example, thioredoxin-interacting protein (TXNIP) matches the arrestin N domain [ PMID: 18664266 , PMID: 23519408 ]. (ebi.ac.uk)
- One α-arrestin, thioredoxin-interacting protein (Txnip), has crucial functions in regulating glucose uptake and glycolytic flux through the mitochondria. (semanticscholar.org)
Activation6
- However, none of these studies have addressed the question of why the β-arrestin-bound, internalized receptor would be required for activation of ERK1/2 when other signals transduced by the receptor occur while it is still at the cell surface. (rupress.org)
- The purpose of the present investigation was to define the role of β-arrestin-containing scaffolding complexes in the activation and subcellular localization of ERK1/2. (rupress.org)
- While my current focus is on arrestin signaling following dopamine receptor activation by ligand, I believe I will be branching out to new topics and hope to gain as much exposure to the workings of lab as possible in 8 weeks time. (duke.edu)
- Furthermore, we previously demonstrated that stimulation of PAR-2 resulted in prolonged activation of ERK1/2 in pseudopodia in a β-arrestin-dependent manner and β-arrestins were required in PAR-2 mediated ERK1/2 activation at the membrane and cell migration in metastatic tumor cell lines, suggesting β-arrestin-dependent ERK1/2 activation might play a role in cell motility. (escholarship.org)
- We hypothesized that β-arrestins behave similar to Ras for β-arrestin-dependent ERK activation to relieve autoinhibition of c-Raf. (escholarship.org)
- Therefore, binding of β-arrestin-1 to c-Raf might ensure formation of scaffolding complex containing β-arrestin-1 and the ERK cascade and play a critical role to activate c-Raf in β-arrestin-dependent ERK1/2 activation. (escholarship.org)
Antibodies1
- A common epitope on S-antigen (arrestin), a potent autoantigen inducing experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor alpha (hTNF alpha) was revealed using two monoclonal antibodies to S-antigen which inhibit EAU induction. (uni-regensburg.de)
ARR31
- 32 Arrestin 3, Retinal (X-Arrestin) (ARR3) Antikörper von 11 Herstellern verfügbar auf www.antikoerper-online.de. (antikoerper-online.de)
Knockdown3
- siRNA-mediated knockdown of β-arrestin 1 or 2 in failing CF decreased the expression of α-smooth muscle actin, suggesting that β-arrestins play an important role in the transformation of CF to activated myofibroblasts in the failing ventricle. (ahajournals.org)
- Knockdown of β-arrestin 1 or 2 in failing CF led to increased β-agonist-stimulated cAMP production and restoration of β-agonist-mediated inhibition of collagen synthesis similar to normal CF. This effect was greater with decreased b-arrestin 2 expression. (ahajournals.org)
- β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. (biologists.org)
Mediate1
- We recently showed that β-arrestin can also mediate β 1 AR transactivation of the EGFR, resulting in a cardioprotective effect under conditions of chronic catecholamine stimulation ( 3 ). (pnas.org)
Localization3
- Localization of the arrestin binding locus to the clathrin terminal domain, J Biol Chem 272 (23), 15017-15022(1997). (springer.com)
- While the PPxY motifs of ARRDC3 are essential for its endosomal localization, only one PPxY motif as well as the arrestin-like domains are needed for proper localization. (jefferson.edu)
- Thus, formation of a signaling complex comprising PAR2, β-arrestin, raf-1, and activated ERK1/2 might ensure appropriate subcellular localization of PAR2-mediated ERK activity, and thereby determine the mitogenic potential of receptor agonists. (rupress.org)
ERK11
- In contrast, a mutant PAR2 (PAR2δST363/6A), which is unable to interact with β-arrestin and, thus, does not desensitize or internalize, activates ERK1/2 by a distinct pathway, and fails to promote both complex formation and cytosolic retention of the activated ERK1/2. (rupress.org)
ARRDC32
- The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intra" by Xufan Tian, Roshanak Irannejad et al. (jefferson.edu)
- The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intracellular Signaling of the β2-Adrenergic Receptor. (jefferson.edu)
Additionally4
- Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. (harvard.edu)
- Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. (genetex.com)
- Additionally, screening campaigns can be accelerated by conducting ß-arrestin and calcium assays in the same well on same instrument, without need of cell fixation, when using instruments capable of real-time fluorescence and flash chemiluminescence. (technologynetworks.com)
- Additionally, the β‐arrestins have a well‐defined clathrin‐binding motif at the C‐terminal domain [ 10 ]. (embopress.org)
Induces1
- Extracellular alpha-synuclein induces sphingosine S1P1R uncoupled from inhibitory G-protein leaving beta-arrestin signal intact. (antibodies-online.com)
Human Beta Arrestin1
- Antiserum to human Beta arrestin-2 was raised by repeated immunisation of goats with highly purified antigen. (mybiosource.com)
Downstream1
- Surprisingly, β-arrestins are also capable of scaffolding a number of signaling molecules such as c-Src, Akt and ERK in order to initiate G protein-independent signaling downstream of activated 7TMRs. (nih.gov)
Signaling16
- Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. (pnas.org)
- Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also β-arrestin-dependent signaling. (pnas.org)
- However, hepatocyte-specific β-arrestin 2 deficiency did not affect hepatic insulin sensitivity or β-adrenergic signaling. (jci.org)
- Importantly, hepatocyte-specific overexpression of β-arrestin 2 greatly reduced hepatic GCGR signaling and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. (jci.org)
- Pluridimensionality of β-arrestin-dependent signaling at seven-transmembrane receptor (7TMRs). (nih.gov)
- Some of the best-characterized β-arrestin-induced signaling mechanisms are schematically represented. (nih.gov)
- Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling. (nih.gov)
- Biophysical studies aimed at understanding multiple active conformations of the 7TMRs and the β-arrestins have begun to unravel the mechanistic basis for the diverse functional capabilities of β-arrestins in cellular signaling. (nih.gov)
- Although these findings have led to a re-envisioning of heptahelical receptor signaling, little is known about the physiological roles of arrestin-dependent signaling. (aspetjournals.org)
- Nonetheless, recent evidence generated using arrestin knockouts, G protein-uncoupled receptor mutants, and arrestin pathway-selective "biased agonists" is beginning to reveal that arrestin signaling plays important roles in the retina, central nervous system, cardiovascular system, bone remodeling, immune system, and cancer. (aspetjournals.org)
- This study investigates the role of β-arrestin signaling in adult human CF isolated from normal and failing left ventricles. (ahajournals.org)
- Inhibition of β-arrestin signaling in CF may represent a novel approach to inhibit or decrease maladaptive cardiac remodeling following myocardial injury. (ahajournals.org)
- In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction. (diabetesjournals.org)
- We previously reported that an upregulation of GRK2 and a decrease in β-arrestin 2 inhibit insulin-induced stimulation of Akt/eNOS signaling and that GRK2 overactivation may result from an increase in PKC activity in aortas from diabetic mice with hyperinsulinemia ( 14 ). (diabetesjournals.org)
- PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. (aspetjournals.org)
- We used fluorescent protein-tagged optical probes to monitor several consequences of PAR2 signaling, including PIP 2 depletion and β-arrestin translocation in real time. (rupress.org)
SiRNA3
- The Lean aorta relaxation response was reduced to the ob/ob level by pretreatment with an siRNA targeting β-arrestin 2. (diabetesjournals.org)
- B ) Specific siRNA reduced β-arrestin-2 expression, as determined by real-time PCR and Western blotting. (aging-us.com)
- F ) Compared with control siRNA (Csi), siRNA against β-arrestin-2 reduced CC3 expression by 22% and increased BiP expression by 22% in LPS-treated cells. (aging-us.com)