A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals.
A PROTEIN-SERINE-THREONINE KINASE that is found in PHOTORECEPTOR CELLS. It mediates light-dependent PHOSPHORYLATION of RHODOPSIN and plays an important role in PHOTOTRANSDUCTION.
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.-.
The portion of a retinal rod cell situated between the ROD INNER SEGMENT and the RETINAL PIGMENT EPITHELIUM. It contains a stack of photosensitive disk membranes laden with RHODOPSIN.
Substances that are recognized by the immune system and induce an immune reaction.
That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.
The process in which light signals are transformed by the PHOTORECEPTOR CELLS into electrical signals which can then be transmitted to the brain.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Specialized cells in the invertebrates that detect and transduce light. They are predominantly rhabdomeric with an array of photosensitive microvilli. Illumination depolarizes invertebrate photoreceptors by stimulating Na+ influx across the plasma membrane.
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.
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.
Adjustment of the eyes under conditions of low light. The sensitivity of the eye to light is increased during dark adaptation.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Photosensitive proteins in the membranes of PHOTORECEPTOR CELLS such as the rods and the cones. Opsins have varied light absorption properties and are members of the G-PROTEIN-COUPLED RECEPTORS family. Their ligands are VITAMIN A-based chromophores.
A c-jun amino-terminal kinase that is found predominantly within NEURONS of the BRAIN, suggesting a role in stress-induced neuronal APOPTOSIS. Several isoforms of the protein with molecular sizes of 47 kDa and 52 kDa exist due to multiple ALTERNATIVE SPLICING.
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.
Biological action and events that support the functions of the EYE and VISION, OCULAR.
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.
A genus of scallops in the family PECTINIDAE, class BIVALVIA. The shell is usually radially ribbed.
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.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Photosensitive proteins expressed in the ROD PHOTORECEPTOR CELLS. They are the protein components of rod photoreceptor pigments such as RHODOPSIN.
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
The procedures involved in combining separately developed modules, components, or subsystems so that they work together as a complete system. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
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.
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)
A genus of mosquitoes (CULICIDAE) that are known vectors of MALARIA.
A species of mosquito in the genus Anopheles and the principle vector of MALARIA in Africa.
A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.
A discipline or occupation concerned with the study of INSECTS, including the biology and the control of insects.
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.
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.
Family of the suborder HAPLORHINI (Anthropoidea) comprising bipedal primate MAMMALS. It includes modern man (HOMO SAPIENS) and the great apes: gorillas (GORILLA GORILLA), chimpanzees (PAN PANISCUS and PAN TROGLODYTES), and orangutans (PONGO PYGMAEUS).
Photosensitive proteins expressed in the CONE PHOTORECEPTOR CELLS. They are the protein components of cone photopigments. Cone opsins are classified by their peak absorption wavelengths.
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.
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
Bluish-colored region in the superior angle of the FOURTH VENTRICLE floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the PERIAQUEDUCTAL GRAY.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
Strong dependence, both physiological and emotional, upon morphine.

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)

Abstract: : Purpose: Arrestin rapidly binds both in vivo and in vitro to phosphorylated light-activated rhodopsin (P-Rh*), thereby quenching signaling in rods. However, in vivo arrestin apparently stays in the complex with P-Rh* for a long time, at least until P-Rh* decays into phospho-opsin. To identify the mechanism that slows down arrestin dissociation, we studied it in direct binding assay. Methods: Tritiated arrestin was pre-bound to P-Rh* for 5 min at 37oC, then diluted 50-fold and allowed to dissociate on ice. Aliquots were taken every 15 min. and bound arrestin was measured using gel-filtration-based assay. Results: The half-life of the complex was found to be 123 + 7 min, i.e., extremely long. Our recent mutagenesis data suggest that in the process of arrestin binding to P-Rh* the three-element interaction involving beta-strand I, alpha-helix one, and arrestin C-tail is disrupted. One of the released elements, alpha-helix I (residues 100-111), is a typical amphipathic helix closely ...
Abstract: : Purpose: To elucidate the structural basis for arrestins receptor specificity. Four cloned arrestin proteins participate in homologous desensitization of hundreds of G protein-coupled receptors. Although the receptor specificity of the two non-visual arrestins is not known, the specificity of rod and cone arrestins for their respective pigments is inferred from their selective expression in these two types of photoreceptor cells. Recently we found that cone arrestin has a 50-fold lower affinity for phosphorylated light-activated rhodopsin (P-Rh*) than rod visual arrestin (VA). The difference in affinity of bovine and salamander VA for P-Rh* of the corresponding vs the other species is of similar magnitude. Methods: Experimentally the preference of VA for P-Rh* and that of beta-arrestin (BA) for agonist-activated phosphorylated m2 muscarinic cholinergic receptor (P-m2*) can be measured in the direct binding assay. Each arrestin demonstrates about 6-fold higher binding to the ...
Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A. A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet. 1995 Jul;10(3):360-2.. ...
Target AntigenRetinal S antigen Quantity50ulClonePDS1HostMouse ImmunogenPorcine retinal S-antigen (arrestin)Myeloma/fusion partnersBalb/c Ag 8.653 myeloma cellsSpecies ReactivityRat, Cow, Human, PigPurificationProtein GFormatPurified antibody (from supernatant) containing PBS 0.1% sodium azideApplicationsWB, IHC-Fr, IC
Arrestins are ubiquitous adaptor proteins that are implicated in diverse signaling pathways. Arrestins are involved in the regulation of G-protein coupled receptors (GPCRs) via endocytosis and desensitization followed by degradation or recycling of the receptor. There are two β-arrestin homologs in mammals, which are largely redundant and therefore difficult to study. Drosophila has a single β-arrestin, Kurtz (Krz), and hence presents unique opportunities to study the functions of β-arrestin. krz maternal mutants have been shown to cause defects in the gastrulation of Drosophila embryos. These were attributed to effects of Krz on Toll signaling pathway. To investigate the origins of the defects, the early hours of embryo development needed to be examined. One of the main pathways activated during the first hours of gastrulation that enables epithelial remodeling and ventral furrow formation is Fog-Mist signaling. Mist is a GPCR that is activated by Fog, which triggers a cascade of downstream
CCR2 is a well studied chemokine receptor that meets considerable clinical interest. Yet, few studies have been investigating recruitment of β-arrestin to CCR2, with CCL2 as the sole analyzed CCR2 ligand (Aragay et al., 1998; García Lopez et al., 2009). Thus, we report the first study dedicated to the investigation of the effects of different CCR2 ligands on β-arrestin recruitment. We demonstrate that the effects of different CCR2 ligands on β-arrestin recruitment to the receptor are quantitatively and qualitatively distinct from one another. Differences were found in recruitment efficacy, identifying CCL7, CCL8, and CCL13 as partial agonists, with submaximal responses despite full receptor occupancy. Comparing β-arrestin 1 or 2, we found potential bias toward β-arrestin 2 of CCL13 and CCL8, overall weak β-arrestin recruiters. Experiments addressing the decline of the CCR2/β-arrestin interaction over time revealed striking differences between the ligands. Although CCL7-induced ...
G protein-coupled receptors are a large family of signalling molecules that respond to a wide variety of extracellular stimuli. The receptors relay the information encoded by the ligand through the activation of heterotrimeric G proteins and intracellular effector molecules. To ensure the appropriate regulation of the signalling cascade, it is vital to properly inactivate the receptor. 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. 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. Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or arresting its ability to interact with transducin ...
Idiopathic pulmonary fibrosis is a progressive disease that causes unremitting extracellular matrix deposition with resulting distortion of pulmonary architecture and impaired gas exchange. 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. Here, we examine the role of β-arrestin1 and β-arrestin2 in the pathobiology of pulmonary fibrosis. In the bleomycin-induced mouse lung fibrosis model, loss of either β-arrestin1 or β-arrestin2 resulted in protection from mortality, inhibition of matrix deposition, and protected lung function. Fibrosis was prevented despite preserved recruitment of inflammatory cells and fibroblast chemotaxis. However, isolated lung fibroblasts from bleomycin-treated β-arrestin-null mice failed to invade extracellular matrix and displayed altered expression of genes involved in matrix production and ...
β-arrestin2 is well known to function as a scaffold for some MAP kinase modules thereby contributing to the activation of mitogen-activated protein kinases by GPCRs. We investigated activation of MAPKs in spermatozoa upon bourgeonal treatment and found that activation of hOR17-4 leads to phosphorylation of ERK1/2 and p38 MAPK. Interestingly, activated ERK1/2 showed nuclear localization. MAPK activation by GPCR-bound arrestin is generally thought to target the MAPK to specific extranuclear locations (Luttrell, 2003; Lefkowitz and Shenoy, 2005). In spite of this, it was recently shown that β-arrestin2 promotes a subset of ERK1/2-mediated transcriptional responses to lysophosphatidic acid receptor activation (Gesty-Palmer et al., 2005) and β2-adrenergic receptor-mediated nuclear translocation of ERK (Kobayashi et al., 2005). Whether the observed nuclear translocation of β-arrestin2 upon hOR17-4 activation in spermatozoa causes the nuclear translocation of ERK1/2, as in the cases of activated ...
Arrestins play a fundamental role in the regulation and signal transduction of G protein-coupled receptors. Here we describe the crystal structure of cone arrestin at 2.3A resolution. The overall structure of cone visual arrestin is similar to the crystal structures of rod visual and the non-visual …
cAMP is a well studied second messenger that is ubiquitously expressed in mammals. It conducts its function by activating its downstream effectors: protein kinase A (PKA), exchange proteins regulated by cAMP (EPAC) and cyclic nucleotide gated ion-channels. The sole mechanism to inactivate cAMP is through degradation via cyclic-phosphodiesterases (PDEs). The PDEs, especially PDE4s, are involved in many diseases including asthma, chronic obstructive pulmonary disease (COPD) and depression. Therefore, PDEs have been a consistently popular research subject for decades and pharmaceutical companies have devoted considerable effort in developing PDE inhibitors. β-arrestin interacts with PDE4D5 and is a multifunctional protein that plays pivotal roles in signal transduction. It functions as an adaptor protein in the c-Raf/MEK/ERK cascade by interacting with c-Raf and ERK ...
Purified C5AR1 CHO-K1 β-Arrestin GPCR Assay Kit from Creative Biomart. C5AR1 CHO-K1 β-Arrestin GPCR Assay Kit can be used for research.
Purified CCR3 CHO-K1 β-Arrestin GPCR Assay Kit from Creative Biomart. CCR3 CHO-K1 β-Arrestin GPCR Assay Kit can be used for research.
Our recent work established the essential role of β-arrestin in the internalization of the M2 mAChR [9]. The present study extends the observations of previous work and demonstrates that the agonist-promoted down-regulation of M1 and M2 mAChRs is β-arrestin dependent, and that the ubiquitination pattern of β-arrestin has a critical role in the differential down-regulation for M1 vs M2 mAChRs.. It has been previously established in a variety of cell lines that a prolonged activation of M1 or M2 mAChRs induces receptor down-regulation. In agreement with these findings, long-term stimulation of M1 or M2 mAChRs induced receptor down-regulation with the M1 mAChR showing significantly more down-regulation than M2 subtype. This observation suggests that the two subtypes are differentially regulated by endogenous β-arrestins. No down-regulation of either mAChR subtype occurred in the absence of β-arrestin and either β-arrestin subtype was able to rescue receptor down-regulation.. The observations ...
Rationale: MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate gene expression. First transcribed as long primary miR transcripts (pri-miRs), they are enzymatically processed in the nucleus by Drosha into hairpin intermediate miRs (pre-miRs) and further processed in the cytoplasm by Dicer into mature miRs where they regulate cellular processes following activation by a variety of signals such as those stimulated by β-adrenergic receptors (βARs). Initially discovered to desensitize βAR signaling, β-arrestins are now appreciated to transduce multiple effector pathways independent of G protein-mediated second messenger accumulation, a concept known as biased signaling. We previously showed that the β-arrestin-biased βAR agonist carvedilol activates cellular pathways in the heart. Objective: Here, we tested whether carvedilol could activate β-arrestin-mediated miR maturation, thereby providing a novel potential mechanism for its cardioprotective ...
The nuclear translocation of ERKs is normally regulated by the phosphorylation status of MEK1 (Whitmarsh and Davis, 1999). MEK1 binds to ERKs and prevents nuclear translocation of ERKs by its nucleus export signal. Phosphorylation of MEK1 leads to the activation of ERKs and the dissociation of MEK1-ERK complexes, which results in the subsequent nuclear translocation of activated ERKs. In several Gq-coupled GPCR systems, the G protein-dependent pathway activates ERKs through PKC, and the activated ERKs translocate into the nucleus, whereas the β-arrestin functions as a scaffold for both MEK1 and ERKs, thereby preventing the nuclear translocation of β-arrestin-activated ERKs (Tohgo et al., 2002; Shenoy and Lefkowitz, 2005). In addition, the prevention of the nuclear translocation of β-arrestin-activated ERKs is related to the interaction between receptor and β-arrestin. With the reduction in receptor-β-arrestin interaction allowing the recycling of the internalized receptor, a certain amount ...
Cardiac fibroblasts (CF) produce and degrade extracellular matrix and are critical in regulating myocardial remodeling which can lead to heart failure. β-arrestins regulate G protein-coupled receptor (GPCR) function and also mediate GPCR-independent signaling. This study investigates the role of β-arrestin signaling in adult human CF isolated from normal and failing left ventricles. β-arrestin-1 expression is increased 1.5-fold in failing CF relative to normal controls. 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. This effect was more pronounced by decreasing β-arrestin 1 expression. 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 ...
We have previously shown that fMLP, C3a, and C5a stimulated CCL2 production in a human mast cell line, HMC-1 (8). We suggested that chemoattractant receptor-induced ERK phosphorylation interacts synergistically with Ca2+/calcineurin-dependent activation of NFAT to induce chemokine gene expression (8). Receptor phosphorylation by GRK and subsequent β-arrestin-mediated internalization via clathrin-coated pits is an important mechanism for activation of ERK by a number of G protein-coupled receptors (27, 28). This raises the possibility that chemoattractant receptor-induced chemokine production could involve receptor phosphorylation and β-arrestin-dependent ERK activation. To test this possibility, transient transfectants were generated in RBL-2H3 cells coexpressing C3aR or ΔST-C3aR and βarr2-GFP conjugate. As shown in Fig. 4⇓A, C3a caused a rapid translocation of βarr2-GFP from the cytosol to the membrane in C3aR cells. In contrast, C3a did not induce this response in ΔST-C3aR cells. PTX, ...
We have previously shown that fMLP, C3a, and C5a stimulated CCL2 production in a human mast cell line, HMC-1 (8). We suggested that chemoattractant receptor-induced ERK phosphorylation interacts synergistically with Ca2+/calcineurin-dependent activation of NFAT to induce chemokine gene expression (8). Receptor phosphorylation by GRK and subsequent β-arrestin-mediated internalization via clathrin-coated pits is an important mechanism for activation of ERK by a number of G protein-coupled receptors (27, 28). This raises the possibility that chemoattractant receptor-induced chemokine production could involve receptor phosphorylation and β-arrestin-dependent ERK activation. To test this possibility, transient transfectants were generated in RBL-2H3 cells coexpressing C3aR or ΔST-C3aR and βarr2-GFP conjugate. As shown in Fig. 4⇓A, C3a caused a rapid translocation of βarr2-GFP from the cytosol to the membrane in C3aR cells. In contrast, C3a did not induce this response in ΔST-C3aR cells. PTX, ...
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. 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. With decades of experience and hundreds of customer publications, DiscoverX provides a complete set of tools to analyze β-arrestin biology. The PathHunter β-arrestin assays and reagents offer a powerful and universal screening and profiling platform that can be used for virtually any Gi-, Gs-, or Gq-coupled receptor ...
Using Drosophila as a model system, Lee and Montell uncovered a surprising divergence between the pathway leading to light-induced blindness and that underlying retinal degeneration. In many vertebrates, sustained exposure to even low-intensity light leads to blindness, which has long been attributed to the retinal degeneration that takes place under these conditions. Lee and Montell showed that Drosophila exposed to continuous light also displayed a progressive reduction in the visual response (measured with an electroretinogram), as well as retinal degeneration. The photoresponse was substantially reduced after 9 days of exposure to continuous light and drastically reduced--or abolished--after 17 days of exposure. Western analysis of head extracts indicated that the concentration of Rh1, the major rhodopsin, declined in parallel with attenuation of the photoresponse, whereas that of various other signaling proteins did not. Genetic analysis revealed that mutations in arrestin (which encodes a ...
Mdm2 is a ubiquitin-protein ligase known to ubiquitinate p53, promoting its degradation by the ubiquitin-proteasome system. Shenoy and co-workers showed that Mdm2 can act as a key factor in the sequestration of the cell surface β2-adrenergic receptor (β-AR) through interactions with β-arrestin. Strous and Schantl discuss how Mdm2 may be a switch connecting extracellular signals mediated through G protein-coupled receptors (GPCRs) to p53 and its functions in apoptosis and cell cycle progression.. ...
Fingerprint Dive into the research topics of β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. Together they form a unique fingerprint. ...
Starting research in the Caron lab has been an exciting, yet terrifying experience. As the recipient of prestigious awards such as the Lieber Prize for Outstanding Achievement in Schizophrenia Research, Dr. Caron has set the standards high for his lab.. Upon first arriving, I was thrown in at the deep end and expectations were high. I witnessed many procedures and took notes as I watched, hoping that I would be able to replicate the techniques on my own when needed. Such is the case with transfecting and splitting cells, which is how I spent most of my time in lab this past week. While my mentor, Tom Pack, no longer has to overbook the hood for me (though he still does just in case), I find that I still have much to learn in the next 7 weeks.. As the summer progresses, I hope to not only increase my technical proficiency in lab, but also gain a greater understanding of GPCR signaling and the lab equipment that exists for studying it. While my current focus is on arrestin signaling following ...
In cardiac fibroblasts and MEFs, our data indicate that the α1ARs make the primary contribution to ERK activation, supporting the dominant roles of these receptor subtypes in cardiac remodeling.34 Consistent with previous studies,35 stimulation of the α1ARs with Phe induces the classic Gq-dependent activation of PLC and PKC, leading to ERK activation through Raf-MEK1 kinase cascade. Under this signaling cascade, activated ERK translocates to the nucleus.35 Interestingly, this scenario is completely reshaped when β2ARs are coactivated with the α1AR on Epi stimulation. Coactivation of the α1 and β2ARs leads to sequestration of phospho-ERK within the cytosol. Under Epi stimulation, it was possible that two pools of ERK existed; a transient pool activated by the β2AR and a prolonged pool activated by the α1AR. The first pool becomes dominant simply because β2ARs are more prominent in cardiac tissues than α1ARs. This explanation is unlikely for several reasons. First, α1AR antagonist ...
By contrast, specific inhibition of endogenous GRK2 by dominant-negative mutants robustly inhibited OTR phosphorylation and internalization as well as arrestin/OTR interactions ...
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The complete amino acid sequence of bovine S antigen (48-kDa protein) has been determined by cDNA and partial amino acid sequencing. A 1623-base-pair (bp) cDNA contains an open reading frame coding for a protein of 404 amino acids (45,275 Da). Tryptic peptides and cyanogen bromide peptides of native bovine S antigen were purified and partially sequenced. All of these peptides were accounted for in the long open reading frame. Searching of the National Biomedical Research Foundation data bank revealed no extensive sequence homology between S antigen and other proteins. However, there are local regions of sequence similarity with alpha transducin, including the sites subject to ADP-ribosylation by Bordetella pertussis and cholera toxins and the phosphoryl binding-sites. Secondary structure prediction and circular dichroic spectroscopy show that S antigen is composed predominantly of beta-sheet conformation. Acid-catalyzed methanolysis suggests the presence of low levels of carbohydrate in the ...
In the current study, the most important question was whether GRK2 negatively controlled the insulin-induced Akt/eNOS pathway in aortas from diabetic mice with hyperinsulinemia. An important vascular action of insulin is its vasodilator effect, which is associated with increased NO production by endothelial cells (4,5,22,23). The results shown in the present Fig. 1A and B are consistent with our previous report (14). In that previous report, we discussed why GRK2 was increased in the diabetic aorta and how it affected the dysfunction of the endothelium-dependent relaxation to insulin that is mediated via the Akt pathway. We drew the conclusion that PKC activation mediated GRK2 overactivation and that the upregulation of GRK2 led to inhibition of the insulin-induced stimulation of the Akt/eNOS pathway (14). In the current study, we were interested in the pathway downstream of GRK2. From the results, we can propose that GRK2 acts by competing for β-arrestin 2 upon insulin-induced Akt/eNOS ...
• Experimental autoimmune uveitis was observed following the adoptive transfer of T cell lymphocytes (T cells) from Lewis rats previously immunized with a small
Mollusks and human are different species, but because of convergent evolution that led them to have similar genetic expression. There have been studies that proved octopus eyes are similar to humans. In their study, they used a set of 1052 genes of the octopus eye and 13 303 genes of the human eye. For one of the research, they discovered that the protein in the eye were similar. When then compared the genes, they identified that a total of 729 genes were commonly expressed, a total of 69.3%. On other various tests,they found that six3, lhx2, retinal arrestin, retinal dehydrogenase, and human nuclear-transport receptor karyopherin were found to be expressed in the octopus eye ...
The varied behavioral effects of kappa opioid receptors (KOR) are mediated through different signaling cascades. KOR activation of G protein-dependent signaling results in analgesia, whereas the dysphoric effects are mediated by a different pathway involving G protein-coupled receptor kinase (GRK) and arrestin. Therefore, a partial KOR agonist that does not efficiently activate arrestin-dependent signaling may produce analgesia without dysphoria. No selective KOR partial agonists are currently available, and preclinical assessment is complicated by sequence differences between rodent (r) and human (h) KOR. KOR antagonists are also of therapeutic interest for their potential anxiolytic and antidepressant effects, but many KOR antagonists have long durations of action resulting from selective activation of cJun kinase (JNK). In this thesis, I compared the signaling events initiated by agonist stimulation of hKOR and rKOR. Although a partial agonist at both hKOR and rKOR, pentazocine was more ...
Figure 1. Immunolocalization of CNTFRα in the adult mouse retina. A: Negative control. B: Pattern of immunoenzymatic labeling with the anti-chick CNTFRα antibody. C: Pattern of immunoenzymatic labeling with the anti-rat CNTFRα antibody. D: Sequential section (to B) labeled with mouse cone arrestin antibody. E: Immunofluorescence labeling (overlaid images) with the anti-chick CNTFRα antibody (green), DAPI (blue), and peanut agglutinin (red). Intense labeling with the CNTFRα antibodies (B,E) was limited to ganglion cells, nerve fibers, and cells located predominantly at the vitreal and scleral borders of the inner nuclear layer (INL). Less intense labeling was also present at the inner plexiform layer (IPL) and outer plexiform layer (OPL). Nonspecific staining was observed at the photoreceptor layer (A-C) and was distinct from the specific cone inner segment labeling (arrows in D) obtained with the mouse cone arrestin antibody. Fluorescence immunocytochemistry confirmed the absence of ...
Ubiquitously reduced signaling via Methuselah (MTH), a G-protein-coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signalling in specific tissues remains unknown. We determined that reduced expression of mth targeted to the insulin-producing cells (IPCs) of the fly brain was sufficient to extend life and enhance oxidative stress resistance. Paradoxically, we discovered that overexpression of mth targeted to the same cells has similar phenotypic effects to reduced expression due to MTHs interaction with β-arrestin, which uncouples GPCRs from their G-proteins. We confirmed the functional relationship between MTH and β-arrestin by finding that IPC-targeted overexpression of β-arrestin alone mimics the longevity phenotype of reduced MTH signaling. As reduced MTH signaling also inhibits insulin secretion from the IPCs, the most parsimonious mechanistic explanation of ...
Heptahelical G protein-coupled receptors are the most diverse and therapeutically important family of receptors in the human genome. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by arrestin binding, which uncouples the receptor and G protein and targets the receptor for internalization. It is clear, however, that heptahelical receptor signaling does not end with desensitization. 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. 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 ...
Figure 12. GPCR and heterotrimeric G-protein signalling.. The ligand bound to the GPCR is shown in red. Binding allows the exchange of GDP for GTP by the associated G protein, and dissociation of the protein into Gα and Gβγ subunits. These then have downstream effects on a range of proteins, thereby propagating the signal from the bound ligand. Yellow arrows indicate either activation (up arrow) or inhibition (down arrow) of the targets. Regulators of G-protein signalling (RGS) proteins aid the GTPase activity of the G protein to turn off the signal. Arrestin can bind the receptor following GPCR phosphorylation by G-protein receptor kinase (GRK), desensitizing the receptor to further signalling. Reproduced from Berridge, M.J. (2012) Cell Signalling Biology; doi:10.1042/csb0001002, with permission. ...
In this study, we have adopted a proteomic approach to characterize new ligands of the TCR‐signaling ITAM motifs. In this way, we identified the GPCR‐interacting protein β‐Arr1 as a novel direct ligand of the TCR that is recruited to unphosphorylated ITAMs in a manner dependent on TCR triggering. While β‐Arr1 was previously described as a cytoplasmic effector of both GPCRs and RTKs (Hupfeld & Olefsky, 2007), this is the first demonstration of β‐Arr1 binding to the TCR, a multi‐subunit receptor without intrinsic enzymatic activity. We found that β‐Arr1 recruitment to the TCR was induced by TCR triggering. However, in contrast to the recruitment of other TCR signaling effectors, such as the tyrosine kinase ZAP‐70 or the adaptor protein Nck (Gil et al, 2002), that is mediated by changes in the TCR itself, recruitment of β‐Arr1 to the TCR was mediated by modifying β‐Arr1. The mechanism by which TCR triggering induces the recruitment of β‐Arr1 to non‐triggered TCRs ...
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InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015 ...
Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation. Binds to the photoreceptor conserved element-I (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter.
TXNIP is a member of the α-arrestin family that functions as an intracellular scaffold, which participates in cellular signaling by formation of signaling complexes and localization of signaling components in the cell.11,12 VEGF-VEGFR2 signaling in EC seems to be dependent on TXNIP as shown in the present study. We showed previously that TXNIP was required for VEGFR2 activation and EC survival in response to low concentrations of H2O2 and tumor necrosis factor-α.15 These data support our concept that TXNIP plays a critical role in regulating VEGFR2 signaling and angiogenesis in EC.. A novel finding of the present study is that TXNIP seems to be required for the earliest stage of VEGFR2 internalization. Receptor tyrosine kinases are regulated by endocytosis through the internalization of plasma membrane receptors.25-27 For example, the internalization of epidermal growth factor receptor is mediated by clathrin-mediated endocytosis and is essential for sustained epidermal growth factor receptor ...
Although many different mutations in humans and Drosophila cause retinal degeneration, in most cases, a molecular mechanism for the degeneration has not been found. We now demonstrate the existence of stable, persistent complexes between rhodopsin and its regulatory protein arrestin in several diffe …
TY - JOUR. T1 - Distinct CCK-2 Receptor Conformations Associated with β-Arrestin-2 Recruitment or Phospholipase-C Activation Revealed by a Biased Antagonist. AU - Magnan, Rémi. AU - Escrieut, Chantal. AU - Gigoux, Véronique. AU - De, Kavita. AU - Clerc, Pascal. AU - Niu, Fan. AU - Azema, Joelle. AU - Masri, Bernard. AU - Cordomi, Arnau. AU - Baltas, Michel. AU - Tikhonova, Irina G. AU - Fourmy, Daniel. PY - 2013/2/20. Y1 - 2013/2/20. N2 - Seven-transmembrane receptors (7TMRs), also termed G protein-coupled receptors (GPCRs), form the largest class of cell surface membrane receptors, involving several hundred members in the human genome. Near 30% of marketed pharmacological agents target 7TMRs. 7TMRs adopt multiple conformations upon agonist binding. Biased agonists, in contrast to non-biased agonists, are believed to stabilize conformations preferentially activating either G-protein- or ß-arrestin-dependent signalling pathways. However, proof that cognate conformations of receptors display ...
TY - JOUR. T1 - β-arrestin-biased agonism of β-adrenergic receptor regulates Dicer-mediated microRNA maturation to promote cardioprotective signaling. AU - Teoh, Jian Peng. AU - Bayoumi, Ahmed S.. AU - Aonuma, Tatsuya. AU - Xu, Yanyan. AU - Johnson, John A.. AU - Su, Huabo. AU - Weintraub, Neal L.. AU - Tang, Yaoliang. AU - Kim, Il Man. PY - 2018/5. Y1 - 2018/5. N2 - Rationale: MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate target genes. First transcribed as primary miR transcripts (pri-miRs), they are enzymatically processed by Drosha into premature miRs (pre-miRs) and further cleaved by Dicer into mature miRs. Initially discovered to desensitize β-adrenergic receptor (βAR) signaling, β-arrestins are now well-appreciated to modulate multiple pathways independent of G protein signaling, a concept known as biased signaling. Using the β-arrestin-biased βAR ligand carvedilol, we previously showed that β-arrestin1 (not β-arrestin2)-biased β1AR ...
3. Berchiche Y.A., Gravel S., Pelletier M-E.,Ste-Onge G., Heveker N. Different effects of the different natural CCR2 ligands on β-arrestin recruitment, Gαi signalling and receptor internalization.(2011) Molecular Pharmacology 79(3):488-98. http://www.ncbi.nlm.nih.gov/pubmed/21088225. 4. Gravel S. Malouf C., Boulais P., Berchiche Y.A., Oishi S., Fujii N., Leduc R., Sinnett D., Heveker N. The Peptidomimetic CXCR4 antagonist TC14012 Recruits Beta-Arrestin to CXCR7-Roles of Receptor Domains.(2010) Journal of Biological Chemistry 285(49):37939-43. http://www.ncbi.nlm.nih.gov/pubmed/20956518. 5. Kalatskaya I*, Berchiche Y.A.*, Gravel S, Limberg B. J., Rosenbaum J.S, Heveker N. AMD3100 is a CXCR7 Ligand with Allosteric Agonist Properties. (2009) Molecular Pharmacology 75:1-8. * Contributed equally to this work. http://www.ncbi.nlm.nih.gov/pubmed/19255243. 6. Rafei M., Berchiche Y.A., Birman E., Boivin MN., Young Y.K., Wu J. H., Heveker N., Galipeau J. An Engineered GMCSF-CCL2 Fusokine is a Potent ...
The mechanism of PAR1 activation is strikingly irreversible. Cleavage of PAR1 by thrombin is irrevocable, and the tethered ligand generated cannot diffuse away from the receptor. In the absence of the reversible ligation that characterizes most receptor systems, how is PAR1 shut off? The β2-adrenergic receptor has served as a prototype for dissecting the molecular events responsible for G protein-coupled receptor desensitization and resensitization (10-13). Upon activation, β2-adrenergic receptor is rapidly phosphorylated. It then binds arrestin, preventing further interaction with G proteins. Arrestin also mediates internalization of β2-adrenergic receptors via clathrin-coated pits (14, 15). Within an endosomal compartment, receptors dissociate from ligand, are dephosphorylated, and recycle back to the cell surface competent to signal again. Thus trafficking serves to remove activated β2-adrenergic receptors from the cell surface and to return the receptors to the surface in an off state, ...
Zhu X, Brown B, Li A et al. (2003). GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina.. J. Neurosci. 23 (14): 6152-60. PMID 12853434. CS1 održavanje: Eksplicitna upotreba et al. (link) ...
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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 ...
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 ...
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 ...
Shiina T, Kawasaki A, Nagao T, Kurose H (Sep 2000). "Interaction with beta-arrestin determines the difference in ...
Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990): β-Arrestin: a protein that regulates β-adrenergic receptor ... While working with Robert Lefkowitz at Duke University he discovered beta-arrestins, proteins that regulate the function of ...
Arrestin. *Oguchi disease 1. Myelin. *Pelizaeus-Merzbacher disease. *Dejerine-Sottas disease. *Charcot-Marie-Tooth disease 1B, ...
"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 ...
Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating ... In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2- ... Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β- ... arrestins (β-arr).[37] Once bound, β-arrestins both sterically prevent G-protein coupling and may recruit other proteins, ...
"GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling". Cell. 166 (4): 907-919. doi:10.1016/j.cell. ...
"Lipid G Protein-coupled Receptor Ligand Identification Using β-Arrestin Path Hunter™ Assay". Journal of Biological Chemistry ...
Beta arrestin has been shown to form complexes with MAP kinase, leading to activation of Extracellular signal-regulated kinases ... While beta arrestin plays a role in receptor desensitization, it may also be critical in mediating downstream effects of ... D2 receptor signaling may mediate protein kinase B, arrestin beta 2, and GSK-3 activity, and inhibition of these proteins ... Beta Arrestin recruitment is mediated by G-protein kinases that phosphorylate and inactivate dopamine receptors after ...
In addition, proteins called arrestins bind metarhodopsin and prevent it from activating more Gq. A sodium-calcium exchanger ...
... has been shown to interact with KPNB1[9][10] and Arrestin beta 1.[11] ... interacts with beta-arrestin 1B". FEBS Letters. 527 (1-3): 71-5. doi:10.1016/S0014-5793(02)03164-2. PMID 12220636.. ...
Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L, Qin L, Ma L, Pei G (February 2003). "Beta-arrestin 2 functions as a G-protein-coupled ... Wang P, Wu Y, Ge X, Ma L, Pei G (March 2003). "Subcellular localization of beta-arrestins is determined by their intact N ...
δ−opioid receptors have been shown to interact with β2 adrenergic receptors,[31] arrestin β1[32] and GPRASP1.[33] ... Cen B, Yu Q, Guo J, Wu Y, Ling K, Cheng Z, Ma L, Pei G (Mar 2001). "Direct binding of beta-arrestins to two distinct ... resulting in beta-arrestin- and clathrin-mediated receptor internalization". The Journal of Biological Chemistry. 276 (7): 4709 ...
Which Do Not Recruit β-Arrestin-2". Journal of Medicinal Chemistry. 59 (18): 8381-97. doi:10.1021/acs.jmedchem.6b00748. PMC ...
Which Do Not Recruit β-Arrestin-2". J. Med. Chem. 59 (18): 8381-97. doi:10.1021/acs.jmedchem.6b00748. PMC 5344672. PMID ...
Lefkowitz, R.J. & Whalen, E.J. (2004). Beta-arrestins: traffic cops of cell signaling. Curr. Opin. Cell Biol., 16, 162-168. ... 25,0 25,1 Luttrell LM, Lefkowitz RJ (February 2002). "The role of beta-arrestins in the termination and transduction of G- ... New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J. Biol. Chem., 273, 18677-18680. ... Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG (2000). "The interaction of β-arrestin with the AP-2 adaptor is required for ...
... more specifically arrestin beta 2.[80][81]. Role of lipophilicityEdit. A set of ligands were evaluated. For agonists, a highly ... "Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo". Proceedings of the ...
Zuo Z (September 2005). "The role of opioid receptor internalization and beta-arrestins in the development of opioid tolerance ...
2003). "Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4". Science 301 (5638): 1391 ...
"Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking ... "Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking ...
The use of bioluminescence resonance energy transfer 2 to study neuropeptide Y receptor agonist-induced beta-arrestin 2 ...
2001). "Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin ...
Gao ZG, Jacobson KA (2008). „Translocation of arrestin induced by human A(3) adenosine receptor ligands in an engineered cell ...
... and beta-arrestin.". J. Biol. Chem. 276 (45): 42182-90. PMID 11535606. doi:10.1074/jbc.M107323200.. CS1 одржавање: Експлицитна ...
... and Arrestin-2 (also termed Arrestin beta 1 or β-arrestin). The GRKs, along with the DAG-activated PKCs, phosphorylate DP2 to ... promote its internalization while arrestin-2 inhibits DP2 from further activating heterotrimeric G proteins while also linking ...
2003). "GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in ...
In addition to its role in Alzheimer's disease, presenilin-1 also found to be important in cancer. A study of broad range gene expression was conducted on human malignant melanoma. Researchers classified the malignant melanoma cell lines into two types. The study showed that presenilin-1 is down regulated in cell type while it is overexpressed in the other cell type.[27] Another study on multidrug resistance (MDR) cell line also reveals a role of presenilin-1 in cancer development. Because of the development to the resistance to chemical, MDR cells become a critical factor on the success of cancer chemotherapy.[28] In the study, researchers tried to explore the molecular mechanism by looking into the expression of Notch1 intracellular (N1IC) domain and presenilin 1. They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 (ABCC1) was also found to be regulated by N1IC, which suggest a mechanism of ABCC1 regulated by presenilin 1 and notch ...
Ankylosing spondylitis: A version of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. It is uncertain how HLA-B27 causes this increased risk. Researchers speculate that HLA-B27 may abnormally display to the immune system peptides that trigger arthritis. Other research suggests that joint inflammation characteristic of this disorder may result from improper folding of the HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. Although most patients with ankylosing spondylitis have the HLA-B27 variation, many people with this particular variation never develop the disorder. Other genetic and environmental factors are likely to affect the chances of developing ankylosing spondylitis and influence its progression. HLA-B27 is associated with the spondyloarthropathies, a group of disorders that includes ankylosing spondylitis and other inflammatory joint diseases. Some of these diseases are associated with a common skin condition ...
PathHunter® β-Arrestin Assays Largest Portfolio of β-Arrestin Cell-based Assays and Reagents for Drug Discovery. β-Arrestins ... PathHunter β-Arrestin Principle for GPCR Applications. PathHunter GPCR β-Arrestin assays take advantage of DiscoverXs ... Ultimate Flexibility - Create Your Own GPCR β-Arrestin Cell-based Assays in Any Cell Type. Create your own GPCR β-arrestin cell ... DiscoverX provides a complete set of tools to analyze β-arrestin biology. The PathHunter β-arrestin assays and reagents offer a ...
Arrestins comprise a family of closely-related proteins that includes beta-arrestin-1 and -2, which regulate the function of ... Cone photoreceptors C-arrestin (arrestin-X) [(PUBMED:7720881)], which could bind to phosphorylated red/green opsins; and ... Arrestin_N. PFAM accession number:. PF00339. Interpro abstract (IPR011021):. G protein-coupled receptors are a large family of ... Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated ...
β-arrestin-1 expression is increased 1.5-fold in failing CF relative to normal controls. siRNA-mediated knockdown of β-arrestin ... This effect was more pronounced by decreasing β-arrestin 1 expression. Knockdown of β-arrestin 1 or 2 in failing CF led to ... This effect was greater with decreased b-arrestin 2 expression. β-arrestin 1 knockdown led to a significant decline in TGF-β- ... Decreased β-arrestin 1or 2 expression in failing CF also led to a decline in MMP-2 expression and activity which plays a key ...
β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix ... β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix ... β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix ... β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix ...
No Rest with Arrestin. Posted on June 18, 2017 by Ian Levitan , Leave a comment ... While my current focus is on arrestin signaling following dopamine receptor activation by ligand, I believe I will be branching ...
Because arrestins preferentially bind to some, but not all, GPCRs in a ligand-dependent manner, we envision that arrestins may ... Arrestin Modulation of Cellular ERK Signaling via GPCR Crosstalk Is a General Mechanism. To test whether this arrestin-mediated ... Arrestin can potentially "prime" phosphatases (PPS) to dephosphorylate α1AR-induced ERK. This arrestin-ERK complex sequesters α ... Activation of the β2AR leads to arrestin recruitment and subsequent β2AR internalization. The β2AR-bound arrestin assembles a ...
Drosophila has a single β-arrestin, Kurtz (Krz), and hence presents unique opportunities to study the functions of β-arrestin. ... Arrestins are involved in the regulation of G-protein coupled receptors (GPCRs) via endocytosis and desensitization followed by ... There are two β-arrestin homologs in mammals, which are largely redundant and therefore difficult to study. ... Arrestins are ubiquitous adaptor proteins that are implicated in diverse signaling pathways. ...
FLAG-tagged β-arrestin 1 and 2, YFP-β-arrestin-2-Ub, β-arrestin 2K11R, K12R, and β-arrestin 2K18R, K107R, K108R, K207R, K296R ( ... pcDNA3.1 FLAG β-arrestin 1 or 2, pEYFP β-Arr-Ub, pcDNA3.1 FLAG β-arrestin 2K11R, K12R, and pcDNA3.1 FLAG β-arrestin 2K18R, ... wild-type β-arrestin 2 or β-arrestin 2K11R, K12R (Figure 11). It is clear, however, that β-arrestin 2K18R, K107R, K108R, K207R ... MEF KO1/2 cells were transfected with eGFP-M1 (A) or HA-M2 (B) mAChRs and either no β-arrestin, FLAG-β-arrestin 2 or YFP-β- ...
Fingerprint Dive into the research topics of β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. ... β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. ...
A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Fuchs S, Nakazawa M, ... Maw M, Tamai M, Oguchi Y, Gal A. A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease ...
4⇓, D and E). These findings suggest that although receptor phosphorylation is required for β-arrestin recruitment, it is not ... Expanding roles for β-arrestins as scaffolds and adapters in GPCR signaling and trafficking. Curr. Opin. Cell Biol. 13: 139. ... β-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290: 1574. ... β-arrestin-dependent formation of β2 adrenergic receptor-Src protein kinase complexes. Science 283: 655. ...
beta-arrestin, MEK1, peptide array, beta2 adrenergic receptor, PDE4D5, RACK1, SUMOylation. Subjects:. Q Science , QH Natural ... β-arrestin interacts with PDE4D5 and is a multifunctional protein that plays pivotal roles in signal transduction. It functions ...
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 ...
... 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 ...
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 ...
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.
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] [ ...
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 ...
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 ...
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. ...
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 ...
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.. 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 ...
... 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 ...
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. ...
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 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 ...
There are no specific protocols for Recombinant Human Arrestin C protein (ab116769). Please download our general protocols ...
Rabbit polyclonal beta Arrestin 1 antibody validated for WB, IP, IHC, ICC/IF and tested in Mouse and Rat. Referenced in 2 ... Beta Arrestin 1 was immunoprecipitated using 0.5mg Mouse Brain tissue lysate, 5µg of Rabbit polyclonal to Beta Arrestin 1 and ... Anti-beta Arrestin 1 antibody. See all beta Arrestin 1 primary antibodies. ... Lanes 2-4 : Anti-beta Arrestin 1 antibody (ab31868) at 1 µg/ml. Lane 2 : Mouse Brain at 20 µg. Lane 3 : Mouse brain tissue ...
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 ...
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. By Laura M. Bohn, Robert J. Lefkowitz, Raul R. Gainetdinov, Karsten ... Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2. By Laura M. Bohn, Robert J. Lefkowitz, Raul R. Gainetdinov, Karsten ...
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. ...
... 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
... β-arrestins 1 and 2. This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular ...
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. ...
Compare Arrestin-S ELISA Kits from AMSBIO LLC from leading suppliers on Biocompare. View specifications, prices, citations, ... Arrestin-S ELISA Kits from AMSBIO LLC. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool ...
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 ...
Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence Nature. 2000 Dec 7;408( ... Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic ... Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu- ... However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase ...
Browse our beta-Arrestin 1 ELISA Kits all backed by our Guarantee+. ... beta-Arrestin 1 ELISA Kits available through Novus Biologicals. ...
Invitrogen Anti-S-arrestin Polyclonal, Catalog # PA1-731. Tested in Western Blot (WB) and Immunofluorescence (IF) applications ... rod arrestin; Rod photoreceptor arrestin; S-AG; S-antigen; retina and pineal gland (arrestin); S-arrestin; S-arrestin short ... Cite S-arrestin Polyclonal Antibody. The following antibody was used in this experiment: S-arrestin Polyclonal Antibody from ... Western blot on recombinant bovine visual arrestin using Product # PA1-731.. Published figure using S-arrestin polyclonal ...
The arrestins are also now known as protein scaffolding platfo ... Non-visual arrestins were initially appreciated for the roles ... Previous Document: GPCRs and Arrestins in Airways: Implications for Asthma.. Next Document: ?-Arrestins: Regulatory Role and ... Non-visual arrestins were initially appreciated for the roles they play in the negative regulation of G protein-coupled ... The arrestins are also now known as protein scaffolding platforms that act downstream of multiple types of receptors, ensuring ...
  • The PathHunter β-arrestin assays and reagents offer a powerful and universal screening and profiling platform that can be used for virtually any G i -, G s -, or G q -coupled receptor. (discoverx.com)
  • 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)
  • 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)
  • Arrestins are involved in the regulation of G-protein coupled receptors (GPCRs) via endocytosis and desensitization followed by degradation or recycling of the receptor. (umb.edu)
  • Moreover, abrogation of β-arrestin ubiquitination has been reported to inhibit receptor internalization with minimal effects on receptor degradation. (jmolecularsignaling.com)
  • Based on this observation, we were interested in examining the effects of disruption of potential ubiquitination sites in the β-arrestin sequence on receptor down-regulation. (jmolecularsignaling.com)
  • Agonist-promoted internalization of the M 2 mAChR was not affected by expression of β-arrestin lysine mutants lacking putative ubiquitination sites, β-arrestin 2 K18R, K107R, K108R, K207R, K296R , while down-regulation and stable co-localiztion of the receptor with this β-arrestin lysine mutant were significantly reduced. (jmolecularsignaling.com)
  • Interestingly, expression of β-arrestin 2 K18R, K107R, K108R, K207R, K296R increased the agonist-promoted down-regulation of the M 1 mAChR but did not result in a stable co-localiztion of the receptor with this β-arrestin lysine mutant. (jmolecularsignaling.com)
  • This phosphorylation allows the binding of β-arrestins (III) which promotes homologous desensitization and subsequent internalization of the receptor into clathrin coated pits. (jmolecularsignaling.com)
  • 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)
  • Sustained agonist-promoted ubiquitination of β-arrestin has been correlated with increased stability of the GPCR - β-arrestin complex. (jmolecularsignaling.com)
  • Arrestins are ubiquitous adaptor proteins that are implicated in diverse signaling pathways. (umb.edu)
  • 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)
  • 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)
  • 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)
  • Using the β-arrestin assays, you can eliminate the need to load target cells prior to every experiment, eliminate the use of radioactivity, and reduce the number of workflow steps, increasing the efficiency of the lab. (discoverx.com)
  • The product comes with a complete set of retroparticles and reagents combined with an easy-to-follow protocol to help you generate your own β-arrestin cell-based assays. (discoverx.com)
  • Drosophila has a single β-arrestin, Kurtz (Krz), and hence presents unique opportunities to study the functions of β-arrestin. (umb.edu)
  • Herein we report that agonist activation of M 1 mAChRs produces a sustained β-arrestin ubiquitination but no stable co-localization with β-arrestin. (jmolecularsignaling.com)
  • In contrast, sustained ubiquitination of β-arrestin by activation of M 2 mAChRs does result in stable co-localization between the M 2 mAChR and β-arrestin. (jmolecularsignaling.com)
  • Given the ubiquitination status of β-arrestin following agonist treatment, we sought to determine the effects of β-arrestin ubiquitination on M 1 and M 2 mAChR down-regulation. (jmolecularsignaling.com)
  • These findings indicate that ubiquitination of β-arrestin has a distinct role in the differential trafficking and degradation of M 1 and M 2 mAChRs. (jmolecularsignaling.com)
  • A constitutively ubiquitinated β-arrestin 2 chimera in which ubiquitin is fused to the C-terminus of β-arrestin 2 (YFP-β-arrestin 2-Ub) significantly increased agonist-promoted down-regulation of both M 1 and M 2 mAChRs, with the effect substantially higher on the M 2 mAChR. (jmolecularsignaling.com)
  • There are two β-arrestin homologs in mammals, which are largely redundant and therefore difficult to study. (umb.edu)
  • However, isolated lung fibroblasts from bleomycin-treated β-arrestin-null mice failed to invade extracellular matrix and displayed altered expression of genes involved in matrix production and degradation. (sciencemag.org)
  • Retroviral Particles - Create target-specific, stable β-arrestin cell lines in any divided cell type. (discoverx.com)
  • These data implicate β-arrestins as mediators of fibroblast invasion and the development of pulmonary fibrosis, and as a potential target for therapeutic intervention in patients with idiopathic pulmonary fibrosis. (sciencemag.org)
  • 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)
  • 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)
  • 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)
  • Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. (abcam.com)
  • Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. (abcam.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)
  • 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. (genetex.com)
  • 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)
  • 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. (mybiosource.com)
  • 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)
  • Furthermore, TCR triggering provokes the β‐arrestin‐1‐mediated downregulation of the G‐protein coupled chemokine receptor CXCR4, but not of other control receptors. (embopress.org)
  • Activated T‐cell receptors (TCRs) employ β‐arrestin‐mediated internalization to downregulate migratory chemokine receptors, but surprisingly also to recruit unliganded peripheral TCRs to the immunological synapse. (embopress.org)
  • Two different modes of arrestin-mediated internalization occur. (abcam.com)
  • 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)
  • 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)
  • The present study explores the mechanisms of GR internalization and the role of PKCα, GPCR kinases (GRKs) and β-arrestins therein. (ovid.com)
  • 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)
  • 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)
  • A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. (axonmedchem.com)
  • Using dominant‐negative and knockdown approaches we demonstrate that β‐arrestin‐1 is required for the internalization and downregulation of non‐engaged bystander TCRs. (embopress.org)
  • Unlike most μ-opioid agonists, herkinorin does not promote the recruitment of β-arrestin-2 to the intracellular domain of the μ-opioid receptor, or induce receptor internalization. (wikipedia.org)
  • 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)
  • In vertebrate rod photoreceptors, rod arrestin quenches the light-induced phototransduction cascade by binding preferentially to the light-activated, phosphorylated rhodopsin. (springer.com)
  • 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)
  • Among potential causes is the endocytosis of stable complexes formed between rhodopsin and its regulatory protein arrestin in certain mutants. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Tools & Resources / Publications & References / Publications / Measurement of β-Arrestin Recruitment for GPCR Targets. (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)
  • 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 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)
  • 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)
  • Activation of the GPCR-PK induces β-Arrestin-EA recruitment, forcing complementation of the two β-galactosidase enzyme fragments (EA and PK). (creativebiomart.net)
  • 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)
  • These data establish structural evidences for distinct conformations of a 7TMR associated with ß-arrestin-2 recruitment or G-protein coupling and validate relevance of the design of biased ligands able to selectively target each functional conformation of 7TMRs. (qub.ac.uk)
  • 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)
  • β‐arrestins 1 and 2 mediate clathrin‐dependent endocytosis of the β 2 AR [ 18 , 19 , 20 ]. (embopress.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Biased agonists, in contrast to non-biased agonists, are believed to stabilize conformations preferentially activating either G-protein- or ß-arrestin-dependent signalling pathways. (qub.ac.uk)
  • 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)
  • This reveals functions for the arrestins Art5/Ygr068c and Art4/Rod1, and additional roles for Art1/Ldb19, Art2/Ecm21 and Art8/Csr2. (nih.gov)
  • These findings strongly suggest that the functional roles of β-arrestins are much broader than currently understood. (nih.gov)
  • Multifaceted roles of β-arrestins and GRKs in 7TMR signaling and regulation. (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)
  • Surprisingly, several α-arrestins play prominent roles in the regulation of metabolism and obesity. (semanticscholar.org)
  • 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)
  • The critical roles of β‐arrestins are demonstrated by the perinatal lethality of β‐arrestin1/β‐arrestin2 double knockout mice and defects observed in single knockout mice for 7TMR‐stimulated responses [ 3 ]. (embopress.org)
  • These novel functions involve the roles for β-arrestins as scaffolds. (escholarship.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. (abcam.com)
  • 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)
  • In conjunction withbiochemical and mutagenesis data, we propose a molecular mechanism bywhich arrestin is activated for receptor binding. (embl.de)
  • 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)
  • 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)
  • 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)
  • G protein subunits, RGS, arrestins, GRKs …) to the activated receptor or conformational changes within their preassembled or newly formed complexes ( 6 - 10 ). (frontiersin.org)
  • On www.antibodies-online.com are 98 Arrestin, beta 2 (ARRB2) Antibodies from 23 different suppliers available. (antibodies-online.com)
  • 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)
  • 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)
  • Synthetic peptide derived from within residues 350 - 450 of Human beta Arrestin 1. (abcam.com)
  • The PA1-731 immunizing peptide corresponds to amino acid residues 2-18 from rat visual arrestin. (thermofisher.com)
  • Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. (ebi.ac.uk)
  • 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)
  • Localization of the arrestin binding locus to the clathrin terminal domain, J Biol Chem 272 (23), 15017-15022(1997). (springer.com)
  • Additionally, the β‐arrestins have a well‐defined clathrin‐binding motif at the C‐terminal domain [ 10 ]. (embopress.org)
  • 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)
  • Interestingly, β-arrestin 2 knockdown did not have this effect, demonstrating specificity for regulating TGF-β-stimulated collagen synthesis. (ahajournals.org)
  • β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. (biologists.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu-opioid receptor to the development of morphine antinociceptive tolerance and the subsequent onset of physical dependence. (nih.gov)
  • Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic morphine treatment, and that these animals fail to develop antinociceptive tolerance. (nih.gov)
  • 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)
  • β-arrestins are adaptor molecules that have been first described in playing a role in G-protein-coupled receptor (GPCR) desensitization. (biologists.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • The arrestin superfamily: cone arrestins are a fourth family. (ebi.ac.uk)
  • Antiserum to human Beta arrestin-2 was raised by repeated immunisation of goats with highly purified antigen. (mybiosource.com)
  • In addition, AP-2 associates with the receptor-arrestin complex in perinuclear endosomes and is required for proper post-endocytic GPCR trafficking. (pubmedcentralcanada.ca)
  • 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)
  • 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)
  • 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)
  • 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)
  • Therefore, β-arrestin-mediated signaling constitutes an important part of GPCR signaling in addition to G protein-mediated signaling. (discoverx.com)
  • 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)
  • 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)