Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.
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 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 family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. They are regulatory proteins that play a role in G-protein-coupled receptor densensitization.
A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.
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.
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.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS. It may play an essential role in regulating myocardial contractile response.
A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Small oviparous fishes in the family Cyprinodontidae, usually striped or barred black. They are much used in mosquito control.
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.
The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.
A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.
A G-protein-coupled receptor kinase subtype that is primarily expressed in the MYOCARDIUM and may play a role in the regulation of cardiac functions.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
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.
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.
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.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.
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.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
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 process in which light signals are transformed by the PHOTORECEPTOR CELLS into electrical signals which can then be transmitted to the brain.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Established cell cultures that have the potential to propagate indefinitely.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
Substances that are recognized by the immune system and induce an immune reaction.
Specialized PHOTOTRANSDUCTION neurons in the vertebrates, such as the RETINAL ROD CELLS and the RETINAL CONE CELLS. Non-visual photoreceptor neurons have been reported in the deep brain, the PINEAL GLAND and organs of the circadian system.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
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.

Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. (1/1016)

Internalization of agonist-activated G protein-coupled receptors is mediated by non-visual arrestins, which also bind to clathrin and are therefore thought to act as adaptors in the endocytosis process. Phosphoinositides have been implicated in the regulation of intracellular receptor trafficking, and are known to bind to other coat components including AP-2, AP180 and COPI coatomer. Given these observations, we explored the possibility that phosphoinositides play a role in arrestin's function as an adaptor. High-affinity binding sites for phosphoinositides in beta-arrestin (arrestin2) and arrestin3 (beta-arrestin2) were identified, and dissimilar effects of phosphoinositide and inositol phosphate on arrestin interactions with clathrin and receptor were characterized. Alteration of three basic residues in arrestin3 abolished phosphoinositide binding with complete retention of clathrin and receptor binding. Unlike native protein, upon agonist activation, this mutant arrestin3 expressed in COS1 cells neither supported beta2-adrenergic receptor internalization nor did it concentrate in coated pits, although it was recruited to the plasma membrane. These findings indicate that phosphoinositide binding plays a critical regulatory role in delivery of the receptor-arrestin complex to coated pits, perhaps by providing, with activated receptor, a multi-point attachment of arrestin to the plasma membrane.  (+info)

Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells. (2/1016)

Arrestin proteins play a key role in the desensitization of G protein-coupled receptors (GPCRs). Recently we proposed a molecular mechanism whereby arrestin preferentially binds to the activated and phosphorylated form of its cognate GPCR. To test the model, we introduced two different types of mutations into beta-arrestin that were expected to disrupt two crucial elements that make beta-arrestin binding to receptors phosphorylation-dependent. We found that two beta-arrestin mutants (Arg169 --> Glu and Asp383 --> Ter) (Ter, stop codon) are indeed "constitutively active." In vitro these mutants bind to the agonist-activated beta2-adrenergic receptor (beta2AR) regardless of its phosphorylation status. When expressed in Xenopus oocytes these beta-arrestin mutants effectively desensitize beta2AR in a phosphorylation-independent manner. Constitutively active beta-arrestin mutants also effectively desensitize delta opioid receptor (DOR) and restore the agonist-induced desensitization of a truncated DOR lacking the critical G protein-coupled receptor kinase (GRK) phosphorylation sites. The kinetics of the desensitization induced by phosphorylation-independent mutants in the absence of receptor phosphorylation appears identical to that induced by wild type beta-arrestin + GRK3. Either of the mutations could have occurred naturally and made receptor kinases redundant, raising the question of why a more complex two-step mechanism (receptor phosphorylation followed by arrestin binding) is universally used.  (+info)

Real-time visualization of the cellular redistribution of G protein-coupled receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the substance P receptor. (3/1016)

The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) and beta-arrestins. The temporal relationship of these proposed biochemical events has never been established for any GPCR other than rhodopsin beyond the resolution provided by biochemical assays. We investigate the real-time activation and desensitization of the human SPR in live HEK293 cells using green fluorescent protein conjugates of protein kinase C, GRK2, and beta-arrestin 2. The translocation of protein kinase C betaII-green fluorescent protein to and from the plasma membrane in response to substance P indicates that the human SPR becomes activated within seconds of agonist exposure, and the response desensitizes within 30 s. This desensitization process coincides with a redistribution of GRK2 from the cytosol to the plasma membrane, followed by a robust redistribution of beta-arrestin 2 and a profound change in cell morphology that occurs after 1 min of SPR stimulation. These data establish a role for GRKs and beta-arrestins in homologous desensitization of the SPR and provide the first visual and temporal resolution of the sequence of events underlying homologous desensitization of a GPCR in living cells.  (+info)

Internalization of the TXA2 receptor alpha and beta isoforms. Role of the differentially spliced cooh terminus in agonist-promoted receptor internalization. (4/1016)

Thromboxane A2 (TXA2) potently stimulates platelet aggregation and smooth muscle constriction and is thought to play a role in myocardial infarction, atherosclerosis, and bronchial asthma. The TXA2 receptor (TXA2R) is a member of the G protein-coupled receptor family and is found as two alternatively spliced isoforms, alpha (343 residues) and beta (407 residues), which share the first 328 residues. In the present report, we demonstrate by enzyme-linked immunosorbent assay and immunofluorescence microscopy that the TXA2Rbeta, but not the TXA2Ralpha, undergoes agonist-induced internalization when expressed in HEK293 cells as well as several other cell types. Various dominant negative mutants were used to demonstrate that the internalization of the TXA2Rbeta is dynamin-, GRK-, and arrestin-dependent in HEK293 cells, suggesting the involvement of receptor phosphorylation and clathrin-coated pits in this process. Interestingly, the agonist-stimulated internalization of both the alpha and beta isoforms, but not of a mutant truncated after residue 328, can be promoted by overexpression of arrestin-3, identifying the C-tails of both receptors as necessary in arrestin-3 interaction. Simultaneous mutation of two dileucine motifs in the C-tail of TXA2Rbeta did not affect agonist-promoted internalization. Analysis of various C-tail deletion mutants revealed that a region between residues 355 and 366 of the TXA2Rbeta is essential for agonist-promoted internalization. These data demonstrate that alternative splicing of the TXA2R plays a critical role in regulating arrestin binding and subsequent receptor internalization.  (+info)

The absence of a direct correlation between the loss of [D-Ala2, MePhe4,Gly5-ol]Enkephalin inhibition of adenylyl cyclase activity and agonist-induced mu-opioid receptor phosphorylation. (5/1016)

Chronic activation of the mu-opioid receptor (MOR1TAG) results in the loss of agonist response that has been attributed to desensitization and down-regulation of the receptor. It has been suggested that opioid receptor phosphorylation is the mechanism by which this desensitization and down-regulation occurs. When MOR1TAG was stably expressed in both neuroblastoma neuro2A and human embryonic kidney HEK293 cells, the opioid agonist [D-Ala2,MePhe4, Gly5-ol]enkephalin (DAMGO) induced a time- and concentration-dependent phosphorylation of the receptor, in both cell lines, that could be reversed by the antagonist naloxone. Protein kinase C can phosphorylate the receptor, but is not involved in DAMGO-induced MOR1TAG phosphorylation. The rapid rate of receptor phosphorylation, occurring within minutes, did not correlate with the rate of the loss of agonist-mediated inhibition of adenylyl cyclase, which occurs in hours. This lack of correlation between receptor phosphorylation and the loss of response was further demonstrated when receptor phosphorylation was increased by either calyculin A or overexpression of the G-protein receptor kinases. Calyculin A increased the magnitude of MOR1TAG phosphorylation without altering the DAMGO-induced loss of the adenylyl cyclase response. Similarly, when mu- and delta-opioid (DOR1TAG) receptors were expressed in the same system, overexpression of beta-adrenergic receptor kinase 2 elevated agonist-induced phosphorylation for both receptors. However, in the same cell lines under the same conditions, overexpression of beta-adrenergic receptor kinase 2 and beta-arrestin 2 accelerated the rate of DPDPE- but not DAMGO-induced receptor desensitization. Thus, these data show that phosphorylation of MOR1TAG is not an obligatory event for the DAMGO-induced loss in the adenylyl cyclase regulation by the receptor.  (+info)

Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis. (6/1016)

Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.  (+info)

The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. (7/1016)

betaarrestins mediate the desensitization of the beta2-adrenergic receptor (beta2AR) and many other G protein-coupled receptors (GPCRs). Additionally, betaarrestins initiate the endocytosis of these receptors via clathrin coated-pits and interact directly with clathrin. Consequently, it has been proposed that betaarrestins serve as clathrin adaptors for the GPCR family by linking these receptors to clathrin lattices. AP-2, the heterotetrameric clathrin adaptor protein, has been demonstrated to mediate the internalization of many types of plasma membrane proteins other than GPCRs. AP-2 interacts with the clathrin heavy chain and cytoplasmic domains of receptors such as those for epidermal growth factor and transferrin. In the present study we demonstrate the formation of an agonist-induced multimeric complex containing a GPCR, betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells. Moreover, beta2-adaptin translocates from the cytosol to the plasma membrane in response to the beta2AR agonist isoproterenol and colocalizes with beta2AR in clathrin-coated pits. Finally, expression of betaarrestin 2 minigene constructs containing the beta2-adaptin interacting region inhibits beta2AR endocytosis. These findings point to a role for AP-2 in GPCR endocytosis, and they suggest that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes of membrane receptors.  (+info)

Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. (8/1016)

Previous studies have demonstrated that beta-arrestin1 serves to target G protein-coupled receptors for internalization via clathrin-coated pits and that its endocytic function is regulated by dephosphorylation at the plasma membrane. Using the yeast two-hybrid system, we have identified a novel beta-arrestin1-binding protein, NSF (N-ethylmaleimide-sensitive fusion protein), an ATPase essential for many intracellular transport reactions. We demonstrate that purified recombinant beta-arrestin1 and NSF interact in vitro and that these proteins can be coimmunoprecipitated from cells. beta-Arrestin1-NSF complex formation exhibits a conformational dependence with beta-arrestin1 preferentially interacting with the ATP bound form of NSF. In contrast to the beta-arrestin1-clathrin interaction, however, the phosphorylation state of beta-arrestin1 does not affect NSF binding. Functionally, overexpression of NSF in HEK 293 cells significantly enhances agonist-mediated beta2-adrenergic receptor (beta2-AR) internalization. Furthermore, when coexpressed with a beta-arrestin1 mutant (betaarr1S412D) that mimics a constitutively phosphorylated form of beta-arrestin1 and that acts as a dominant negative with regards to beta2-AR internalization, NSF rescues the betaarr1S412D-mediated inhibition of beta2-AR internalization. The demonstration of beta-arrestin1-NSF complex formation and the functional consequences of NSF overexpression suggest a hitherto unappreciated role for NSF in facilitating clathrin coat-mediated G protein-coupled receptor internalization.  (+info)

The invention discloses a multifunctional adapter plate which is used for assembling a mechanical finger and multiple tools for cooperation use. The multifunctional adapter plate comprises a first installation plate and a second installation plate which are connected. The first installation plate is used for installing the mechanical finger and provided with a U-shaped sliding groove; sliding rails are arranged on one face of the first installation plate; the mechanical finger can slide along the sliding groove; slopes which enable the mechanical finger to slide therein and are inclined downwards are arranged on the other face of the first installation plate; the slopes are arranged at the opening of the U-shaped sliding groove; the second installation plate is used for installing tools used in cooperation with the mechanical finger; and the second installation plate is provided with an armour clamp installation hole and a plurality of other connecting holes. The multifunctional adapter plate is
The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor.: Endocytosis of the low density lipoprotein (LDL) receptor (LDL
Author(s): Min, Jungah | Advisor(s): DeFea, Kathryn A | Abstract: 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. These novel functions involve the roles for β-arrestins as scaffolds. It has been reported that β-arrestins interact with a number of binding partners including trafficking proteins, cytosolic kinases, cytoskeletal proteins, and non-receptor tyrosine kinase. 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. 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
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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 ...
BACKGROUND AND PURPOSE: Diverse proteases cleave protease-activated receptor-2 (PAR2) on primary sensory neurons and epithelial cells to evoke pain and inflammation. Trypsin and tryptase activate PAR2 by a canonical mechanism that entails cleavage within the extracellular N-terminus revealing a tethered ligand that activates the cleaved receptor. Cathepsin-S and elastase are biased agonists that cleave PAR2 at different sites to activate distinct signalling pathways. Although PAR2 is a therapeutic target for inflammatory and painful diseases, the divergent mechanisms of proteolytic activation complicate the development of therapeutically useful antagonists. EXPERIMENTAL APPROACH: We investigated whether the PAR2 antagonist GB88 inhibits protease-evoked activation of nociceptors and protease-stimulated oedema and hyperalgesia in rodents. KEY RESULTS: Intraplantar injection of trypsin, cathespsin-S or elastase stimulated mechanical and thermal hyperalgesia and oedema in mice. Oral GB88 or par2 ...
In recent years, biased agonists as well as pharmacological chaperones have demonstrated the potential to harness G protein-coupled receptor signaling and trafficking and have collectively opened new...
Acute liver injury can be caused by oxidative stress within a short period and is a common pathway to many liver diseases. The liver is vulnerable to reactive oxygen species (ROS) and free radical-mediated disorders. beta-arresting was initially discovered to be a negative regulator of G protein-coupled receptor signaling. Recently, beta-arresting has been found to act as a multifunctional adaptor protein and play new roles in regulating intracellular signaling networks. However, the role of beta-arresting in the pathogenesis of acute liver injury is unclear. In this study, we hypothesize that beta-arresting regulates acute liver injury via modulation of oxidative stress. beta-arresting knockout mice were used to investigate the impacts of beta-arrestin2 on carbon tetrachloride (CCl4)-induced acute liver injury and oxidative stress. Results here suggested that beta-arresting deficiency decreased serum activities of aminotransferase and alleviated liver injury induced by CCl4 injection as ...
Kurtz (Krz) is the only Drosophila homolog of mammalian beta-arrestins. We have already implicated Krz in regulation of Toll, receptor tyrosine kinase (RTK) and mitogen activated protein kinase (MAPK) pathways. As a multifunctional adaptor, how does Krz coordinate different signaling pathways and carry out well-orchestrated duties? I hypothesize that a possible strategy for Krz is to dynamically reorganize its core interaction complexes in response to the given physiological status. I systematically tested this hypothesis by analyzing in vivo Krz signaling networks dynamics. I also performed an in vivo structure-function analysis of Krz by biochemistry and genetic analysis. I successfully identified the in vivo core Krz interaction complexes, which include: Ulp1, Dos, shep, CG10289 and CG3797; my results suggested phosphoinositide binding elements (KRK motif) in Krz was important for normal fertility of flies, which may due to combined defects of RTK and Toll. As a case study, I also investigated
This study suggests that, unlike the mechanisms of β2 adrenoceptor regulation (Zhang et al., 1997b; Oakley et al., 1999; Gainetdinov et al., 2004), MOR resensitization in LC neurons does not require βarr-2-dependent mechanisms. When MOR endocytosis was presumably impaired by deletion of βarr-2, disruption of GRK2 function, or disruption of dynamin function, MOR resensitization was similarly accelerated rather than inhibited. Furthermore, intracellular application of a phosphatase inhibitor in the absence of βarrestin-dependent receptor trafficking (GRK2 inhibition in βarr-2 k.o.) prevented full recovery of MOR function, suggesting that MOR dephosphorylation is required for MOR resensitization and that this can occur independently of βarr-2-dependent MOR trafficking and endocytosis. The ability of MOR to dephosphorylate and resensitize rapidly when GRK2 and βarr-2 processes are disrupted is consistent with the observation that blocking endocytosis with concanavalin A in cultured LC neurons ...
p130Cas adaptor protein regulates basic procedures such as for example cell cycle control, survival and migration. enough to re-establish branching morphogenesis and regular Erk1/2 MAPK activity. General, these outcomes indicate that high degrees of p130Cas appearance profoundly have an effect on mammary morphogenesis by changing epithelial architecture, success and unbalancing Erk1/2 MAPKs activation in response to development elements and human hormones. These results claim that alteration of morphogenetic pathways because of 701213-36-7 p130Cas over-expression might best mammary epithelium to tumorigenesis. Launch p130Cas, originally defined as an extremely phosphorylated proteins in cells changed by v-Src and v-Crk oncogenes, is normally a multifunctional adaptor proteins necessary Rabbit polyclonal to PID1 for embryonic advancement [1] and it is seen as a structural motifs that enable connections with a number of signaling substances. These multi-protein complexes feeling and integrate ...
p130Cas adaptor protein regulates basic procedures such as for example cell cycle control, survival and migration. enough to re-establish branching morphogenesis and regular Erk1/2 MAPK activity. General, these outcomes indicate that high degrees of p130Cas appearance profoundly have an effect on mammary morphogenesis by changing epithelial architecture, success and unbalancing Erk1/2 MAPKs activation in response to development elements and human hormones. These results claim that alteration of morphogenetic pathways because of 701213-36-7 p130Cas over-expression might best mammary epithelium to tumorigenesis. Launch p130Cas, originally defined as an extremely phosphorylated proteins in cells changed by v-Src and v-Crk oncogenes, is normally a multifunctional adaptor proteins necessary Rabbit polyclonal to PID1 for embryonic advancement [1] and it is seen as a structural motifs that enable connections with a number of signaling substances. These multi-protein complexes feeling and integrate ...
Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to cell surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines and their 20 GPCR targets generates an extensive signaling network to which promiscuity and biased agonism add further complexity. The receptor CXCR4 recognizes both monomeric and dimeric forms of the chemokine CXCL12, which is a distinct example of ligand bias in the chemokine family. We demonstrated that a constitutively monomeric CXCL12 variant reproduced the G protein-dependent and β-arrestin-dependent responses that are associated with normal CXCR4 signaling and lead to cell migration. In addition, monomeric CXCL12 made specific contacts with CXCR4 that are not present in the structure of the receptor in complex with a dimeric form of CXCL12, a biased agonist that stimulates only G protein-dependent signaling. We produced an ...
Kit Component:- KN205534G1, ARRDC4 gRNA vector 1 in pCas-Guide vector- KN205534G2, ARRDC4 gRNA vector 2 in pCas-Guide vector- KN205534D, donor vector…
Description ARRDC1-AS1 Polyclonal Antibody, FITC Conjugated. FITC. Raised in Rabbit. Formulation Liquid. 0.03% Proclin 300, 50% Glycerol, 0.01M PBS, PH 7.4. Specificity Human Isotype IgG Uniprot ID Q9H2J1 Purification >95%,...
Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53 ...
Method and system for transferring data between a computing system and a storage device is provided. The system includes a storage controller including a frame snooper module that detects a TMR and generates a pause signal to a channel that stops the channel from sending any non-data frames to a buffer memory, wherein the channel continues to receive and process data frames while the channel is stopped from sending the command frames to the buffer memory; a counter for counting TMRs; and logic for generating an interrupt if a number of TMRs received exceeds a certain threshold value. The method includes detecting a TMR generating a command to stop a channel from receiving non-data frames while continuing to receive data frames from a Fiber Channel interface; and generating an interrupt to a processor after a certain number of TMRs are received.
Howard Kurtz provides an overview of the MSM coverage of the Downing Street Debacle, but leaves out this gem from Nancy Pelosi, who has become my favorite Congressperson today: She credited blogs for focus on the Downing Street minutes, which...
Howard Kurtz provides an overview of the MSM coverage of the Downing Street Debacle, but leaves out this gem from Nancy Pelosi, who has become my favorite Congressperson today: She credited blogs for focus on the Downing Street minutes, which...
Visit Healthgrades for information on Dr. Kimberly Kurtz, MD Find Phone & Address information, medical practice history, affiliated hospitals and more.
Structural soil is perfect for urban settings for planting trees within sidewalks and other hardscapes. Visit Kurtz Bros. of Columbus, Ohio to learn more.
I was broad awake by this time, but, lying perfectly at ease, remained still, having no inducement to change my position. How did that ivory come all this way? growled the elder man, who seemed very vexed. The other explained that it had come with a fleet of canoes in charge of an English half-caste clerk Kurtz had with him; that Kurtz had apparently intended to return himself, the station being by that time bare of goods and stores, but after coming three hundred miles, had suddenly decided to go back, which he started to do alone in a small dugout with four paddlers, leaving the half-caste to continue down the river with the ivory. The two fellows there seemed astounded at anybody attempting such a thing. They were at a loss for an adequate motive. As to me, I seemed to see Kurtz for the first time. It was a distinct glimpse: the dugout, four paddling savages, and the lone white man turning his back suddenly on the headquarters, on relief, on thoughts of home-perhaps; setting his face ...
Please register to see prices including your discount. Registration may take up to 24h. For guest orders the standard discount of your institution will apply and discounts are visible on the order confirmation.. ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferat
The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which
In het algemeen wordt gekozen voor een in opzet curatieve locoregionale behandeling. De belangrijkste prognostische factoren voor de overleving na salvagebehandeling van een locoregionaal recidief na mastectomie zijn het interval tussen oorspronkelijke behandeling en de grootte of uitbreiding van het recidief [van Tienhoven, 1999 Aberizk, 1986; Mendenhall, 1988; Schwaibold, 1991; Jager, 1998; van der Sangen, 2003]. Ook bij de oorspronkelijke behandeling ongunstige factoren zoals positieve okselklieren [van Tienhoven, 1999; Jager, 1998] en de plaats van het recidief (lokaal of regionaal of beide) worden genoemd als prognostische factor [van der Sangen, 2003]. Ook na MST is het interval de belangrijkste prognostische factor voor het effect van salvagebehandeling, naast de grootte van het recidief, de oorspronkelijke klierstatus en de lokalisatie van het recidief (lokaal of regionaal) [Aberizk, 1986; Osborne, 1994; Voogd, 2005; Elkhuizen, 2001; Kurtz, 1989; Fourquet, 1989; van Tienhoven, 1999; ...
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 ...
βarrestin (βarr)-1 and -2 (βarrs) (or Arrestin-2 and -3, respectively) are universal G protein-coupled receptor (GPCR) adapter proteins expressed abundantly in extra-retinal tissues, including the myocardium. Both were discovered in the lab of the 2012 Nobel Prize in Chemistry co-laureate Robert Lefkowitz, initially as terminators of signaling from the β-adrenergic receptor (βAR), a process known as functional desensitization. They are now known to switch GPCR signaling from G protein-dependent to G protein-independent, which, in the case of βARs and angiotensin II type 1 receptor (AT1R), might be beneficial, e.g., anti-apoptotic, for the heart. However, the specific role(s) of each βarr isoform in cardiac GPCR signaling and function (or dysfunction in disease), remain unknown. The current consensus is that, whereas both βarr isoforms can desensitize and internalize cardiac GPCRs, they play quite different (even opposing in certain instances) roles in the G protein-independent signaling pathways
The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the mu opioid receptor (muOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the muOR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic ...
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
Our study provides evidence for a new role of Src in the phosphorylation of the clathrin adaptor complex AP-2 (via the phosphorylation of the β-subunit, i.e. β2-adaptin). We identify Y737 in the ear domain of β2-adaptin as an important Src target. We show that this residue represents a regulatory site for controlling the dissociation of β-arrestin from AP-2 in clathrin-coated pits (CCPs). Our results not only extend the pleiotropic function of Src in GPCR internalization, but also highlight the importance of receptor-dependent signaling in the clathrin-mediated endocytosis of AT1R.. β-arrestins are multifunctional adaptors involved in the endocytosis and signaling of many GPCRs (Claing et al., 2002; Lefkowitz, 1998). They have been shown to target receptors to CCPs through binding to clathrin and the β-subunit of AP-2 (Goodman, Jr et al., 1996; Laporte et al., 1999), and to act as signal transducers by recruiting different kinases to GPCRs (Luttrell and Luttrell, 2004). We have previously ...
G protein-coupled receptor desensitization and trafficking are important regulators of opioid receptor signaling that can dictate overall drug responsiveness in vivo. Furthermore, different μ-opioid receptor (μOR) ligands can lead to varying degrees of receptor regulation, presumably because of distinct structural conformations conferred by agonist binding. For example, morphine binding produces a μOR with low affinity for β-arrestin proteins and limited receptor internalization, whereas enkephalin analogs promote robust trafficking of both β-arrestins and the receptors. Here, we evaluate μOR trafficking in response to activation by a novel μ-selective agonist derived from the naturally occurring plant product, salvinorin A. It is interesting that this compound, termed herkinorin, does not promote the recruitment of β-arrestin-2 to the μOR and does not lead to receptor internalization. Moreover, whereas G protein-coupled receptor kinase overexpression can promote morphine-induced ...
GPR84 is an orphan G-protein-coupled receptor that is expressed on immune cells and implicated in several inflammatory diseases. The validation of GPR84 as a therapeutic target is hindered by the narrow range of available chemical tools and consequent poor understanding of GPR84 pathophysiology. Here we describe the discovery and characterization of DL-175, a potent, selective, and structurally novel GPR84 agonist and the first to display significantly biased signaling across GPR84-overexpressing cells, primary murine macrophages, and human U937 cells. By comparing DL-175 with reported GPR84 ligands, we show for the first time that biased GPR84 agonists have markedly different abilities to induce chemotaxis in human myeloid cells, while causing similar levels of phagocytosis enhancement. This work demonstrates that biased agonism at GPR84 enables the selective activation of functional responses in immune cells and delivers a high-quality chemical probe for further investigation.
Purpose: : The arrestin-receptor interaction is a complex multi-step process. Arrestins undergo global conformational changes upon binding to their cognate receptors, but the conformation of active, receptor-bound arrestins remains unknown. We identified arrestin-1 elements engaged by different functional forms of rhodopsin and the conformational changes induced by receptor binding. Methods: : We used solution nuclear magnetic resonance (NMR) spectroscopy of 15N-labeled arrestin-1, free and in the presence of light activated (Rh*), phosphorylated light activated rhodopsin (P-Rh*), and phospho-opsin (P-Ops) in bicelles. Results: : Solution NMR was used to assign ~40% of arrestin-1 backbone resonances. Native rhodopsin-containing disc membranes are too large for NMR, whereas detergents that solubilize rhodopsin denature arrestin-1. Bicelles, where bilayered lipid discs are edge-stabilized by detergent, provide a native membrane-like environment for rhodopsin and preserve arrestin-1 structure and ...
GPCRs have important roles in mediating fundamental physiological processes such as vision, olfaction, cardiovascular function, and pain perception. Cellular communication through GPCRs requires the coordination of processes governing receptor activation, desensitization, and resensitization. However, the relative contribution of desensitization mechanisms to the overall homeostatic process still remains largely unexplored in vivo. GPCR kinases (GRKs) act to phosphorylate activated receptors and promote their interaction with β-arrestins. This, in turn, prevents further coupling with G proteins and disrupts normal activation of the second messenger signaling cascade. By this mechanism, GRKs and β-arrestins can act to dampen GPCR signaling, thereby leading to desensitization of the receptor (1). At least six GRKs (GRK1 to GRK6) and four arrestins (visual and cone arrestin, β-arrestins 1 and 2) have been discovered; however, the functional importance of such redundancy is unclear. ...
Thank you for your interest in spreading the word about Science Signaling.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
Thank you for your interest in spreading the word about Science Signaling.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
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 ...
MB12 Nasal Spray Summary. This is a DRAFT document - last updated 03/16/07 The Start of MB12 Nasal Spray and a Disclaimer MB12 Nasal Spray was developed by Stan Kurtz, an independent researcher and father of a child who recovered from autism.. Stan is also NOT A DOCTOR. He is a parent. Further more, many of the conclusions in this document come from parent observations and not scientific study. Several studies about MB12 are in various stages, but little is published to date.. This document is supported with medical literature, scientific data, clinical observation reports, and parental reports. It also reflects the observations, views and personal experience of Stan Kurtz who is a parent (not a doctor). Mr. Kurtzs perspective is driven from his personal experience including his own recovery from irritable bowel and ADHD symptoms. Additionally, it includes information from an evolving data pool of parents in his online group with 30,000 posts from 3000 members, many of which are sharing ...
Jane Kurtz in Philadelphia, PA. Jane Kurtz, CNA specializes in certified registered nurse anesthetist, practices at 800 Spruce Street, phone number, opening hours, doctor nearby.
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 ...
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 ...
The G-protein-coupled receptors (GPCRs, also called seven-transmembrane receptor, 7TMRs, or heptahelical receptor) are a conserved family of seven transmembrane receptors which are essential not only in the healthy heart and blood vessels but also in for treatment and therapy of cardiovascular disease and failure. Heart failure is a global leading cause of morbidity and death and as such understanding 7TMRs, their functions, structures and potential for therapy is essential. This review will investigate the roles of the receptors in the healthy functioning cardiovascular system, and in cardiac disorders with an emphasis in cardiomyopathy. It will also explore the role of autoimmunity and autoantibodies against the G-protein-coupled receptors in cardiomyopathy.. ...
ARRB has been awarded a $200,000 grant from Sustainability Victoria towards a new trial of recycled crushed glass in asphalt on local roads.
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 ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Steve Kurtz: Sometimes comfortably and sometimes uncomfortably. Since some [progressive political art] seemed so issue-driven and party and movement affiliated, we tend not to fit all that well there. We like to keep our independence. I see us as being like an experimental wing, searching for new tools and ways of behaving, new kinds of situations we can create. Some of them work and some of them dont. Hopefully, when we are successful, other movements can pick them up and use them however they feel like it.. So much [progressive political art] seemed separate from its theorization. Much in the way the Situationists were the first [to ask], How do you have real practice and work that is completely theorized at the same time? These two things work hand in hand. Often times this is not the case, you get the artist wanting to act, and the theorist wanting to think. Where does it get together? Because of the conflicts that often come of that rift, we just said, well take care of this in-house, ...
on the methods of Ron Kurtz, creator of the Hakomi Method.. The Refined Hakomi Method, as it is now called, continues to draw its inspiration and power from the healing wisdom of nature and our human capacities for love and awareness. The method embraces the support of science, spirituality and all forms of healing. With study and practice, this simple, elegant way of caring and helping each other is easy to learn and has the power to heal the hearts it touches. Using it is joyous work.. The original version of the Hakomi Method began forty years ago in my private practice in Albany, N.Y. The Refined Method described here is the latest version. After ten years of private practice and some teaching, I founded the Hakomi Institute. During the 1980′s, I ran the Institute. In 1990, I left. During the twenty years since, I have continued to make changes to the method. I dropped some of the original material, like character theory, and added a great deal of new material. The very latest version is ...
DentalPlans detailed profile of Marshall Kurtz , DDS - Dentist in 06810. View plans, sample savings & pricing, patient reviews & practice information.
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
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 ...
NZ | The Australian Road Research Board holds a number of functions throughout the year. Be sure to keep a watch on the next exciting function, where you can network with peers and engage with the industries best and brightest.
Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters.
Concerns about staffing are shared by commission members. I am concerned that if the staffing levels and the funding available to the agency do not keep up with the number and the scope and the complexity of the applications coming down the pipeline, then the jurisdictions sense of place will be lost, said Commissioner Rebecca Kurtz.. Prospective zoning - the delineation of areas where different types and intensities of development are appropriate - and protecting the sense of place in the unorganized territories go hand in hand, she said.. The 1997 comprehensive plan called for prospective zoning in four areas - the Rangeley area, the land around Moosehead Lake, Carrabassett Valley and the Millinocket area.. In the decade after the plan was adopted, the commission was only able to complete prospective zoning in one of those areas - Rangeley.. Kurtz said the commission has an excellent staff, but a lack of prospective zoning means that too often they are negotiating with landowners on where ...
As well as operating a daily humor website, we also publish Timothy McSweeneys Quarterly Concern, Illustoria and an ever-growing selection of books under various imprints. You can buy all of these things from our online store. You can support us today by making a donation ...
Sci Signal. 2008 Nov 25;1(47):ra15. (abstract & full text) Kovacs P, Kress R, Rocha J, Kurtz U, Miquel JF, Nervi F, Méndez-Sánchez N, Uribe M, Bock HH, Schirin-Sokhan R, Stumvoll M, Mössner J, Lammert F, Wittenburg H ...
The Strange Case of Steve Kurtz: Critical Art Ensemble and the Price of Freedom. An interview with Robert Hirsch from After Image Magazine.
The Strange Case of Steve Kurtz: Critical Art Ensemble and the Price of Freedom. An interview with Robert Hirsch from After Image Magazine.
1997). "Arrestin/clathrin interaction. Localization of the arrestin binding locus to the clathrin terminal domain". J. Biol. ...
Differential regulation of beta-arrestins 1 and 2". The Journal of Biological Chemistry. 277 (52): 50422-30. doi:10.1074/jbc. ...
S-arrestin is a protein that in humans is encoded by the SAG gene. Members of arrestin/beta-arrestin protein family are thought ... 1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2 ... S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the ... Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ... GRK/arrestin system serves as a signaling switch for G protein-coupled receptors. GRK4 is most highly expressed in the testes, ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ... GRK5 and the closely related GRK6 phosphorylate receptors at sites that encourage arrestin-mediated signaling rather than ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes ... Feng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI (June 2005). "ATP stimulates GRK-3 phosphorylation and beta-arrestin-2- ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... Phosphorylated serine and threonine residues in GPCRs act as binding sites for and activators of arrestin proteins. Arrestin ... also known as arrestin-4 or X-arrestin. GRK2 was first identified as an enzyme that phosphorylated the beta-2 adrenergic ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ...
Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Thus the ... which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents ... Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell ... Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10: 125. doi: ...
Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser Nature 526: 561-567 T. Hua, K. Vemuri, M ... and the human Rhodopsin-Arrestin complex. 2016: The marijuana receptor-human Cannabinoid receptor type 1 (CB1) and the human C- ...
Bruchas MR, Macey TA, Lowe JD, Chavkin C (June 2006). "Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin- ... β-arrestin antagonist Zyklophin - selective peptide antagonist; dynorphin A analogue Found in numerous species of mint, ( ... β-arrestin antagonist Tifluadom - (atypical) benzodiazepine Nalfurafine (Remitch), which was introduced in 2009, is the first ... β-arrestin antagonist Amentoflavone - non-selective; naturally-occurring AT-076 - non-selective, likely long acting; JDTic ...
... which has been observed for arrestins. Moreover, Vps26 does not have similar sequences as arrestins for GPCR and phospholipid ... Both Vps26 and arrestins are composed of two structurally related β-sheet domains forming extensive interfaces with each other ... Vps26 is a 38-kDa subunit that has a two-lobed structure with a polar core that resembles the arrestin family of trafficking ... Shi H, Rojas R, Bonifacino JS, Hurley JH (2006). "The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C ...
"Prolonged photoresponses in transgenic mouse rods lacking arrestin". Nature. 389 (6650): 505-509. Bibcode:1997Natur.389..505X. ...
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 ...
While it binds to the same receptors as opioid analgesics, TRV734 has very weak β-arrestin recruitment, unlike other available ... Violin, Jonathan D.; Lefkowitz, Robert J. (2007). "Β-Arrestin-biased ligands at seven-transmembrane receptors". Trends in ... ß-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: A novel therapeutic ... but Trevaga hopes to avoid this with TRV250 by bypassing the β-arrestin pathway. TRV734 is an oral follow-up to the injected ...
"S-Nitrosylation of β-Arrestins Biases Receptor Signaling and Confers Ligand Independence". Mol Cell. 70 (3): 473-487. doi: ...
DeGraff JL, Gagnon AW, Benovic JL, Orsini MJ (1999). "Role of arrestins in endocytosis and signaling of alpha2-adrenergic ...
"Spatial regulation of GPR64/ADGRG2 signaling by β-arrestins and GPCR kinases". Annals of the New York Academy of Sciences. 1456 ...
Kim Y, Kim H, Lee J, Lee JK, Min SJ, Seong J, Rhim H, Tae J, Lee HJ, Choo H (August 2018). "Discovery of β-Arrestin Biased ... beta-arrestin recruitment, and receptor internalization. Inactivating antagonists all likely interact with the 5-HT7 receptor ... role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization". Receptors & Channels ...
Kim YM, Barak LS, Caron MG, Benovic JL (May 2002). "Regulation of arrestin-3 phosphorylation by casein kinase II". The Journal ...
Arrestin. *Oguchi disease 1. Myelin. *Pelizaeus-Merzbacher disease. *Dejerine-Sottas disease. *Charcot-Marie-Tooth disease 1B, ...
Arrestin. *Oguchi disease 1. Myelin. *Pelizaeus-Merzbacher disease. *Dejerine-Sottas disease. *Charcot-Marie-Tooth disease 1B, ...
... has been shown to interact with: Arrestin beta 1, Arrestin beta 2, HRAS, KRAS, MRAS, RAP1A, RAP2A, RAPGEF2, and RRAS. ... "Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization". Nat. Cell Biol. 4 (8): 547- ...
In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2- ... Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating ... Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β- ... Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an ...
Reiter, Eric; Ahn, Seungkirl; Shukla, Arun K.; Lefkowitz, Robert J. (11 January 2012). "Molecular Mechanism of β-Arrestin- ... India portal Biology portal Cell signaling Arrestin Membrane proteins Please see Selected bibliography section "Arun K. Shukla ... "Functional specialization of β-arrestin interactions revealed by proteomic analysis". Proceedings of the National Academy of ... "Global phosphorylation analysis of β-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR)". ...
Arrestin-C also known as retinal cone arrestin-3 is a protein that in humans is encoded by the ARR3 gene. arrestin GRCh38: ... "Entrez Gene: ARR3 arrestin 3, retinal (X-arrestin)". Craft CM, Whitmore DH, Wiechmann AF (1994). "Cone arrestin identified by ... Murakami A, Yajima T, Sakuma H, McLaren MJ, Inana G (Dec 1993). "X-arrestin: a new retinal arrestin mapping to the X chromosome ... 2002). "Mouse cone arrestin expression pattern: light induced translocation in cone photoreceptors". Mol. Vis. 8: 462-71. PMID ...
... via protein kinase phosphorylation or b-arrestin-dependent internalization. A study was conducted where a point mutation was ...
van Koppen, C. J.; Jakobs, K. H. Arrestin-Independent Internalization of G Protein-Coupled Receptors. Molecular Pharmacology ... of β-arrestin and the activation of the p38 MAPK and other secondary signaling cascades that are dependent on β-arrestin. INTA ... to form a conformation to block the recruitment of a protein family known as the β-arrestins. These proteins are responsible ...
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 ... arrestin β1 and GPRASP1. κ-opioid receptor μ-opioid receptor GRCh38: Ensembl release 89: ENSG00000116329 - Ensembl, May 2017 ... resulting in beta-arrestin- and clathrin-mediated receptor internalization". The Journal of Biological Chemistry. 276 (7): 4709 ...
Arrestin-3. The second non-visual arrestin cloned was first termed β-arrestin-2 (retroactively changing the name of β-arrestin ... In mammals, arrestin-1 and arrestin-4 are largely confined to photoreceptors, whereas arrestin-2 and arrestin-3 are ubiquitous ... Arrestin-2 was the first non-visual arrestin cloned. It was first named β-arrestin simply because between two GPCRs available ... Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, after ...
Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene. ... Arrestin beta 2 is crucial for the development of tolerance to morphine and other opioids. Arrestin beta 2 has been shown to ... Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high ... Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein- ...
Thus, as with metazoan arrestin, fungal arrestin appears to contribute to 7TMR signaling, and this signaling involves similar ... The N-terminal arrestin domain was responsible for the interaction with the PalH cytoplasmic domain. Growth at alkaline pH was ... S. Herranz, J. M. Rodríguez, H.-J. Bussink, J. C. Sánchez-Ferrero, H. N. Arst, Jr., M. A. Peñalva,O. Vincent, Arrestin-related ... report the identification of a fungal arrestin homolog and its role in pH signaling. PalF, a protein containing C-terminal and ...
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 ...
... 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
... 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 ...
... β-arrestins 1 and 2. This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular ...
Regulation of G protein-coupled receptors by receptor kinases and arrestins.. Sterne-Marr R1, Benovic JL. ...
The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin i … ... Arrestins constitute a superfamily of regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, ... The arrestin superfamily: cone arrestins are a fourth family FEBS Lett. 1995 Apr 3;362(2):247-55. doi: 10.1016/0014-5793(95) ... The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin in Xenopus ...
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 ...
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 ...
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 2 antibody. Validated in WB, IHC and tested in Rat, Human. Cited in 2 publication(s). Immunogen ... Anti-Beta Arrestin 2 antibody. See all Beta Arrestin 2 primary antibodies. ... also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin- ... All lanes : Anti-Beta Arrestin 2 antibody (ab151774) at 0.5 µg/ml. Lane 1 : HeLa Whole Cell Lysate. Lane 2 : Rat Skeletal ...
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. ...
kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila. Gregg Roman, Jin He and Ronald L. Davis ... kurtz, a Novel Nonvisual Arrestin, Is an Essential Neural Gene in Drosophila ...
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. ...
  • Arrestins (abbreviated Arr) are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. (wikipedia.org)
  • In addition to GPCRs, arrestins bind to other classes of cell surface receptors and a variety of other signaling proteins. (wikipedia.org)
  • Arrestins block GPCR coupling to G proteins in two ways. (wikipedia.org)
  • The N-terminal domain consists of an immunoglobulin-like beta-sandwich structure and is found in arrestin and related proteins. (ebi.ac.uk)
  • First characterized as blocking signal transduction by preventing interaction between receptor cytoplasmic domains and heterotrimeric G proteins, arrestins are now known to participate in endocytosis and signaling of 7TM receptors, e.g., by linking them to the endocytic internalization machinery ( 1 , 2 ). (pnas.org)
  • Arrestins comprise a family of closely-related proteins. (ebi.ac.uk)
  • Arrestins constitute a superfamily of regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors. (nih.gov)
  • show that β-arrestins, which limit signaling by GPCRs coupled to G proteins of the G s class, serve a very similar function in control of signaling by M1 muscarinic receptors. (sciencemag.org)
  • In the cases of the manganese transporter Smf1 and the amino acid transporters Can1, Lyp1 and Mup1 it has been shown that ubiquitination is mediated by arrestin-like adaptor proteins that bind to Rsp5 and recognize specific transporters. (nih.gov)
  • The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins 1 . (nature.com)
  • These results reveal, at high resolution, a receptor-interacting interface on β-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins. (nature.com)
  • For example he counts the accessory proteins arrestin and retinoid binding protein, but these can be completely absent in vertebrates with either no effect or mild night blindness eg. (wordnik.com)
  • Arrestins are regulatory proteins that down-regulate phosphorylated G-protein coupled receptors (GPCRs). (springer.com)
  • βarrestins have an analogous function to rod arrestin in the termination of GPCR signaling by sterically inhibiting the coupling of phosphorylated receptors to their respective G proteins. (springer.com)
  • The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). (abcam.com)
  • Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. (pubmedcentralcanada.ca)
  • Beta Arrestin 1 is a member of a family of proteins widely expressed but especially abundant in the central nervous system. (thermofisher.com)
  • Additionally we are shipping Arrestin 3 Kits (40) and Arrestin 3 Proteins (8) and many more products for this protein. (antibodies-online.com)
  • G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. (osti.gov)
  • β‑arrestins are a family of adaptor proteins that regulate the signaling and trafficking of various G protein‑coupled receptors (GPCRs). (spandidos-publications.com)
  • Arrestins bind a host of catalytically active proteins and serve as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into the receptor-arrestin complex. (aspetjournals.org)
  • There are 9903 Arrestin_C domains in 9566 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing Arrestin_C domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with Arrestin_C domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing Arrestin_C domain in the selected taxonomic class. (embl.de)
  • This method is highly amenable to the detection of G protein-coupled receptor (GPCR) interactions with proteins critical for regulating their function, such as β-arrestins. (frontiersin.org)
  • The BRET method utilizes heterologous co-expression of fusion proteins linking one protein of interest (GPCR) to a bioluminescent donor enzyme, a variant of Renilla luciferase, and a second protein of interest (β-arrestin) to an acceptor fluorophore. (frontiersin.org)
  • β-Arrestin 1 and 2 are highly expressed proteins involved in the desensitization of G protein-coupled receptor signaling which also regulate a variety of intracellular signaling pathways. (frontiersin.org)
  • Arrestins are a family of auxiliary proteins associated with GPCRs that consist of four members: visual arrestin (arrestin 1), cone arrestin (arrestin 4), β-arrestin 1 (arrestin 2), and β-arrestin 2 (arrestin 3) ( Patwari and Lee, 2012 ). (frontiersin.org)
  • Activated receptors are subsequently phosphorylated in complex patterns on intracellular domains by serine/threonine G protein-coupled receptor kinases (GRKs), which reduce receptor affinity for G proteins and increase receptor affinity for arrestins ( 7 - 10 ). (pubmedcentralcanada.ca)
  • Furthermore, the discovery of biased GPCR ligands and the findings that distinct G-proteins versus β-arrestin signaling preferences may offer therapeutic advantages over conventional ligands imply that a screening campaign should be designed to focus on the most disease relevant pathways (7-10). (discoverx.com)
  • To understand the role of arrestin in melanopsin function, we investigated the interaction mechanism of these two proteins. (arvojournals.org)
  • GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. (diabetesjournals.org)
  • The classical visual and β-arrestins belong to a larger family of proteins that likely share structural similarity. (semanticscholar.org)
  • Humans have an additional six related proteins sometimes termed the α-arrestins, whose functions are now emerging. (semanticscholar.org)
  • Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. (biologists.org)
  • The Dictyostelium discoideum genome encodes six arrestin-related proteins, harboring additional modules besides the arrestin domain. (biologists.org)
  • Using fluorescently tagged proteins combined with resonance energy transfer and image cross-correlation spectroscopy approaches, we show in live cells that β2-adaptin phosphorylation is an important regulatory process for the dissociation of β-arrestin-AP-2 complexes in CCPs. (biologists.org)
  • Arrestin proteins then bind to the phosphorylated receptor initializing clathrin-mediated internalization. (ahajournals.org)
  • One potential nexus for GPCR signaling crosstalk are the multifunctional scaffold proteins known as arrestins. (ahajournals.org)
  • Arrestins not only scaffold proteins for the activation of different MAPK families under single receptor activation, but also mediate transactivation of epidermal growth factor receptor signaling pathways 2,6 and activation of many other non-GPCR signaling cascades. (ahajournals.org)
  • 7 In the case of GPCR-induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activation, both G proteins and arrestins are capable of mediating ERK activation via independent mechanisms, with each pathway leading to unique spatiotemporal consequences. (ahajournals.org)
  • Arrestins were initially named on the basis of their ability to turn-off the coupling of G protein-coupled receptors (GPCRs) to G proteins and thereby inhibit G protein-dependent GPCR signaling. (elifesciences.org)
  • β‐arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven‐transmembrane receptor trafficking and signalling. (embopress.org)
  • Other proteins with predicted 'arrestin‐like' structural domains but lacking sequence homology have been indicated to function like β‐arrestin in receptor regulation. (embopress.org)
  • The arrestin‐domain‐containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized β 2 AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of β‐arrestin2. (embopress.org)
  • Mammalian cells also express arrestin‐domain‐containing proteins (ARRDC 1-5 and the thioredoxin‐interacting protein TXNIP), which have predicted structural similarities with arrestins but lack sequence homology [ 4 , 5 , 6 , 7 ]. (embopress.org)
  • In yeast, a small family of arrestin‐domain‐containing proteins with PPXY motifs function as arrestin‐related trafficking adaptors for the yeast HECT domain E3 ligase Rsp5, which regulates ubiquitination and trafficking of plasma membrane amino‐acid transporters [ 16 ]. (embopress.org)
  • It has been reported that β-arrestins interact with a number of binding partners including trafficking proteins, cytosolic kinases, cytoskeletal proteins, and non-receptor tyrosine kinase. (escholarship.org)
  • Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. (paperity.org)
  • The data on arrestins and many other multi-functional proteins indicate that in many cases, "order" might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. (paperity.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)
  • In conclusion, this structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology. (osti.gov)
  • Create your own GPCR β-arrestin cell-based assays to evaluate ligand-induced β-arrestin recruitment to any GPCR in any cell type. (discoverx.com)
  • Using the enzyme fragment complementation technology, simply infect your target cells with the PathHunter β-Arrestin Retroparticles, transfect the cells with a GPCR plasmid, and perform a PathHunter GPCR β-arrestin assay with your ligand of interest. (discoverx.com)
  • PathHunter GPCR β-Arrestin assays take advantage of DiscoverX's proprietary Enzyme Fragment Complementation technology. (discoverx.com)
  • The GPCR is fused in frame with a small enzyme donor fragment ProLink™ (PK) and co-expressed in cells stably expressing a fusion protein of β-arrestin and the larger, N-terminal deletion mutant of β-galactosidase (called enzyme acceptor or EA). (discoverx.com)
  • Activation of the GPCR stimulates binding of β-arrestin to the PK-tagged GPCR and forces complementation of the two enzyme fragments, resulting in the formation of an active β-galactosidase enzyme. (discoverx.com)
  • 2009) uncovers a role for beta-arrestin, previously known to control GPCR desensitization, in insulin signaling. (garvan.org.au)
  • Therefore, the enhanced BRET methodology has not only enabled live cell compound screening as we have recently published, it now provides a new level of sensitivity for monitoring specific transient, weak or hardly detectable protein-protein complexes, including agonist-independent GPCR/β-arrestin interactions. (frontiersin.org)
  • GPCR) to a bioluminescent donor enzyme, a variant of Renilla luciferase (luminophore: Rluc, hRluc, Rluc2, or Rluc8), and a second protein of interest (e.g., β-arrestin) to an acceptor fluorophore, a variant of green fluorescent protein (Venus or GFP10). (frontiersin.org)
  • In this study, we show that the interaction of GPCR-bound arrestin with Adaptor Protein 2 (AP-2) is a critical anti-apoptotic event. (pubmedcentralcanada.ca)
  • In addition, AP-2 associates with the receptor-arrestin complex in perinuclear endosomes and is required for proper post-endocytic GPCR trafficking. (pubmedcentralcanada.ca)
  • We propose a model in which the abnormal accumulation of internalized GPCR-arrestin complexes in recycling endosomes, resulting from defective arrestin-AP-2 interactions, leads to the specific initiation of aberrant signaling pathways and apoptosis. (pubmedcentralcanada.ca)
  • Tools & Resources / Publications & References / Publications / Measurement of β-Arrestin Recruitment for GPCR Targets. (discoverx.com)
  • 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)
  • Therefore, β-arrestin-mediated signaling constitutes an important part of GPCR signaling in addition to G protein-mediated signaling. (discoverx.com)
  • There are four major in vitro assay technologies available on the market that are capable of measuring ligand-induced β-arrestin recruitment: PathHunter β-arrestin Assay (DiscoverX) (11), Tango GPCR Assay (Thermo Fisher Scientific) (12), LinkLight GPCR/ β-arrestin Signaling Pathway Assay (BioInvenu) (13), and Transfluor Assay (Molecular Devices) (14). (discoverx.com)
  • The PathHunter β-arrestin Assay, Tango GPCR Assay System and LinkLight GPCR/ β-arrestin Signaling Pathway Assays are homogenous, high throughput assays while the Transfluor Assay is a fluorescence image-based assay. (discoverx.com)
  • All four assays involve the expression of the β-arrestin as a fusion protein with another protein or fragment, while the PathHunter, Tango and LinkLight assays require fusion of the GPCR to another peptide or protein moiety as well. (discoverx.com)
  • β-arrestins regulate G protein-coupled receptor (GPCR) function and also mediate GPCR-independent signaling. (ahajournals.org)
  • MMP-2 expression was upregulated 1.5-fold in failing CF. In conclusion, our results suggest that β-arrestins play an important role in the regulation of collagen synthesis and degradation by CF. This occurs through GPCR (β-AR/cAMP) and GPCR-independent (TGF-β/ERK) mechanisms. (ahajournals.org)
  • GRK2-mediated phosphorylated GPCR promotes the binding of β-arrestin 2, which is reportedly ubiquitously expressed, and then mediates various signal-transduction pathways such as Akt ( 12 ). (diabetesjournals.org)
  • 13 ) reported that insulin stimulates the formation of a new β-arrestin 2 signal complex in which β-arrestin 2 acts as a scaffold for translocation of Akt to IR, even though IR is not a GPCR. (diabetesjournals.org)
  • This assay measures an essential pathway in GPCR activation, i.e. β-arrestin recruitment to activated GPCRs, enabling scientists to screen for and profile functional agonists and inhibitors of GPCRs. (discoverx.com)
  • DiscoveRx has announced the release of the PathHunter™ Flash Detection Kit to enable ß-arrestin recruitment by a GPCR in 30 seconds, permitting screens of up to 1,000,000 compounds in 48 hours. (technologynetworks.com)
  • A ligand-activated, GPCR-arrestin interaction combines two ß-galactosidase fragments, enabling rapid chemiluminescent detection in a homogeneous format. (technologynetworks.com)
  • The present study explores the mechanisms of GR internalization and the role of PKCα, GPCR kinases (GRKs) and β-arrestins therein. (ovid.com)
  • β-Arrestin GPCR cells are engineered to co-the ProLink (PK) tagged GPCR and the Enzyme Acceptor (EA) tagged β-Arrestin. (creativebiomart.net)
  • Activation of the GPCR-PK induces β-Arrestin-EA recruitment, forcing complementation of the two β-galactosidase enzyme fragments (EA and PK). (creativebiomart.net)
  • We have previously shown that stimulation of the angiotensin II (Ang II) type 1 receptor (AGTR1, hereafter referred to as AT1R), a member of the GPCR family, promotes the formation of a complex between β-arrestin, the kinase Src and AP-2. (biologists.org)
  • β-arrestins are adaptor molecules that have been first described in playing a role in G-protein-coupled receptor (GPCR) desensitization. (biologists.org)
  • 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)
  • 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)
  • Because arrestins preferentially bind to some, but not all, GPCRs in a ligand-dependent manner, we envision that arrestins may play a role in GPCR crosstalk by coordinating MAPK activation in distinct subcellular compartments. (ahajournals.org)
  • 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)
  • 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)
  • Arrestin-binding often competes with G-protein for GPCR interaction and constitutes the mechanism of deactivation. (arvojournals.org)
  • A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. (axonmedchem.com)
  • Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers. (wikipedia.org)
  • Arrestin binding to the receptor blocks further G protein-mediated signaling and targets receptors for internalization, and redirects signaling to alternative G protein-independent pathways, such as β-arrestin signaling. (wikipedia.org)
  • Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals, as well as having signalling roles in their own right. (wikipedia.org)
  • Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Regulation of G protein-coupled receptors by receptor kinases and arrestins. (nih.gov)
  • 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)
  • 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)
  • 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)
  • Serving as an adaptor or scaffold molecule, beta Arrestin 1 is essential for mitogenic signaling and mediates agonist-dependent desensitization and internalization of Gprotein-coupled receptors (GPCRs, e.g., beta 2-adrenergic receptor). (thermofisher.com)
  • Beta Arrestin 1 in the cytosol is phosphorylated by ERK1 and 2 on serine412 in a negative feedback mechanism and binds to the phosphorylated receptors at the plasma membrane. (thermofisher.com)
  • β-Arrestins are ubiquitously expressed and function in the activation of GPCRs, desensitization of most 7-transmembrane receptors, and regulation of other signaling molecules such as protein kinases. (discoverx.com)
  • Signaltermination is achieved by the action of the arrestins, which bind toactivated, phosphorylated G protein-coupled receptors. (embl.de)
  • In particular, we were able to show receptor/β-arrestin interactions in an agonist-independent manner using Rluc8-tagged mutant receptors, in contrast to when using Rluc. (frontiersin.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • It was first named β-arrestin simply because between two GPCRs available in purified form at the time, rhodopsin and β2-adrenergic receptor, it showed preference for the latter. (wikipedia.org)
  • The second non-visual arrestin cloned was first termed β-arrestin-2 (retroactively changing the name of β-arrestin into β-arrestin-1), even though by that time it was clear that non-visual arrestins interact with hundreds of different GPCRs, not just with β2-adrenergic receptor. (wikipedia.org)
  • GPCRs and Arrestins in Airways: Implications for Asthma. (biomedsearch.com)
  • Despite their central role in regulation and signalling of GPCRs, a structural understanding of β-arrestin activation and interaction with GPCRs is still lacking. (nature.com)
  • Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. (osti.gov)
  • For GPCRs, ligand-induced β-arrestin recruitment activates signaling cascades independent of G-protein signaling to provide a non-amplified signal which is ideal for antagonist mode screening, studying ligand pharmacologies, and deorphanizing GPCRs. (discoverx.com)
  • It has been demonstrated that β‑arrestins serve roles in various physiological and pathological processes and exhibit a similar function to GPCRs. (spandidos-publications.com)
  • Complex formation between phosphorylated GPCRs, arrestins and an ever-increasing number of effector molecules is known to regulate cellular function. (pubmedcentralcanada.ca)
  • As many GPCRs are found to recruit β-arrestin, the β-arrestin recruitment assay has found important use in drug discovery, especially in the discovery of ligands for orphan GPCRs and in situations where the second messenger signaling is unknown (5,6). (discoverx.com)
  • PathHunter β-Arrestin cell lines are stable clonal cell lines that expedite drug discovery and development by providing robust response to over 90% of all known G-protein coupled receptor (GPCRs), with accurate pharmacology. (discoverx.com)
  • Although, β-arrestin can assume both roles of signaling and endocytic adaptor for many GPCRs, it is still largely unknown whether the recruitment of signaling molecules to β-arrestin impacts its endocytic function. (biologists.org)
  • Collectively, these data show that β-arrestin2 phosphorylation at Thr 383 underlies β-arrestin-dependent Erk1/2 activation by GPCRs. (elifesciences.org)
  • Typically, most GPCRs induce temporally distinct and spatially segregated G protein-dependent and β-arrestin-dependent activation of Erk: G protein-mediated Erk activation is rapid and transient, reaching a maximal level within a few minutes and is followed by translocation of activated Erk into the nucleus to promote gene transcription and cell proliferation. (elifesciences.org)
  • These effects of β-arrestin knockdown on PIP 2 recovery were prevented when serine/threonine phosphatases that dephosphorylate GPCRs were inhibited. (rupress.org)
  • Upon activation, most mammalian GPCRs are phosphorylated in the C-terminal region by G-protein receptor kinases, which serve to recruit arrestin. (arvojournals.org)
  • The arrestin superfamily includes visual arrestins, beta-arrestins (βarrestins) and insect chemosensory arrestins. (springer.com)
  • New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization, J Biol Chem 273 (30), 18677-18680 (1998). (springer.com)
  • Lefkowitz, Shenoy: Transduction of receptor signals by beta-arrestins. (antibodies-online.com)
  • C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways. (sigmaaldrich.com)
  • Expression of two beta-arrestins - Arrb1 and Arrb2 in ipRGCs was analyzed by single cell qPCR. (arvojournals.org)
  • Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination. (semanticscholar.org)
  • METHODS/RESULTS: Using permanent and primary human bronchial epithelial (HBE) cells at air-liquid interface, we show that DEPs activate the human MMP-1 gene via RAS and subsequent activation of RAF-MEK-ERK1/2 mitogen-activated protein kinase signaling, which can be scaffolded by beta-arrestins. (duke.edu)
  • GRK phosphorylation specifically prepares the activated receptor for arrestin binding. (wikipedia.org)
  • By using mutants of the β 1 AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against β-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires β 1 AR phosphorylation at consensus G protein-coupled receptor kinase sites and β-arrestin recruitment to the ligand-occupied receptor. (pnas.org)
  • Turning off the G protein signal by a process known as desensitization occurs through G protein-coupled receptor kinase (GRK) phosphorylation of the 7TMR, and subsequent binding of β-arrestin ( 1 , 2 ). (pnas.org)
  • B ) Insulin-induced phosphorylation of AKT and GSK3α/β remains unaffected by the lack of β-arrestin 2 in hepatocytes. (jci.org)
  • Krishnamurthy, Galet, Ascoli: The association of arrestin-3 with the follitropin receptor depends on receptor activation and phosphorylation. (antibodies-online.com)
  • Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. (harvard.edu)
  • β-arrestin 1 knockdown led to a significant decline in TGF-β-stimulated collagen synthesis in normal and failing CF. This is likely mediated by decreased ERK 1/2 phosphorylation and activation which resulted from β-arrestin 1 knockdown. (ahajournals.org)
  • Although visual arrestin has been shown to quench the catalytic activity of photoexcited, phosphorylated rhodopsin in a reconstituted system, its role in the intact rod cell remains unclear because phosphorylation alone reduces the catalytic activity of rhodopsin. (semanticscholar.org)
  • Duration and amplitude of the light-induced cGMP hydrolysis in vertebrate photoreceptors are regulated by multiple phosphorylation of rhodopsin and by arrestin binding. (semanticscholar.org)
  • Here, we report that formation of such a complex is involved in the AT1R-mediated tyrosine phosphorylation of β2-adaptin, the subunit of AP-2 involved in binding β-arrestin. (biologists.org)
  • We identify a crucial tyrosine residue in the ear domain of β2-adaptin and show in vitro that the phosphorylation of this site regulates the interaction between β-arrestin and β2-adaptin. (biologists.org)
  • We also found a marked decrease in the association of β-arrestin-1 with the IGF-IR and a 55% inhibition of IGF-I-stimulated MAP kinase phosphorylation. (asm.org)
  • In insulin-treated, β-arrestin-1-downregulated cells, there was complete inhibition of lysophosphatidic acid (LPA) or isoproterenol (ISO)-stimulated MAP kinase phosphorylation. (asm.org)
  • Ectopic expression of wild-type β-arrestin-1 in insulin-treated cells in which endogenous β-arrestin-1 had been downregulated rescued IGF-I- and LPA-stimulated MAP kinase phosphorylation. (asm.org)
  • Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. (figshare.com)
  • This phosphorylation barcode is translated into specific β-arrestin conformations that dictate selective signaling and the nature of β-arrestin intracellular functions. (elifesciences.org)
  • Another mechanism that might underlie β-arrestin dependency of receptor-operated signaling is the phosphorylation of β-arrestins themselves. (elifesciences.org)
  • Simulations supported the conclusions that phosphorylation of PAR2 by protein kinases initiates receptor desensitization and that recruited β-arrestin traps the phosphorylated state of the receptor, protecting it from phosphatases. (rupress.org)
  • The strength of arrestin-receptor interaction plays a role in this choice: tighter complexes tend to increase the probability of receptor degradation (Class B), whereas more transient complexes favor recycling (Class A), although this "rule" is far from absolute. (wikipedia.org)
  • The N-terminal arrestin domain was responsible for the interaction with the PalH cytoplasmic domain. (sciencemag.org)
  • Substitution in PalF of a highly conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction and pH signaling in vivo . (pnas.org)
  • What's more, our results suggested that the interaction between β-arrestin 2 and Zbtb46 might negatively regulate DC migration. (jimmunol.org)
  • Using RNA sequencing, we indicated that genes CD74, NR4A1, and ZFP36 might be the target genes regulated by the interaction between β-arrestin 2 and Zbtb46. (jimmunol.org)
  • HEK-293 cells were transiently transfected with full-length or C-terminal truncated melanopsin and arrestin, and its interaction with arrestin was investigated by co-immunoprecipitation assay. (arvojournals.org)
  • Upon interaction with FPR2 expressed by neutrophils both F2Pal10 and WKYMVM activated the PLC-PIP2-Ca2+ signaling pathway and the superoxide-generating NADPH-oxidase, but only WKYMVM activated the receptor to recruit β-arrestin. (ovid.com)
  • Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian β-arrestin family, which is predicted to share similar tertiary structure with visual-/β-arrestins and also contains C-terminal PPxY motifs that mediate interaction with E3 ubiquitin ligases. (jefferson.edu)
  • PAR4SFT supported only 8.74% of PAR4 P2Y12 interaction, abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation. (aspetjournals.org)
  • Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. (figshare.com)
  • non‐visual arrestin 2 and 3) contain a characteristic α‐helix in the N‐terminal domain and a polar core that keeps the molecule constrained in a basal conformation, which is disrupted on arrestin-receptor interaction [ 8 , 9 ]. (embopress.org)
  • We hypothesized that the ability of β-arrestins to scaffold and prolong MAPK signaling at the membrane, is dependent upon precise molecular interactions that are facilitated by interaction of β-arrestins with PAR-2. (escholarship.org)
  • Selective β-arrestin/β2-adaptin interaction inhibitor (IC50 values of 19.1 and 15.6 μM for β-arrestin1 and β-arrestin2, respectively). (axonmedchem.com)
  • Insects have arr1 and arr2, originally termed "visual arrestins" because they are expressed in photoreceptors, and one non-visual subtype (kurtz in Drosophila). (wikipedia.org)
  • 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)
  • 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)
  • To characterize the functional roles of the co-expressed visual arrestins, cone arrestin (Carr) and arrestin1 (Arr1), in mouse cone phototransduction. (arvojournals.org)
  • The recovery of S-dominant murine cones from dim flashes is only modestly affected by the absence of both visual arrestins. (arvojournals.org)
  • To capture this active conformation, we used a conformationally selective synthetic antibody fragment (Fab30) that recognizes the phosphopeptide-activated state of β-arrestin-1. (nature.com)
  • The following antibody was used in this experiment: S-arrestin Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA1-731, RRID AB_2183220. (thermofisher.com)
  • By Western blot this antibody detects an ~57 kDa protein representing recombinant bovine and sheep visual arrestin. (thermofisher.com)
  • The following product was used in this experiment: beta Arrestin 1 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-35089, RRID AB_2552399. (thermofisher.com)
  • There are currently no images for S-arrestin Antibody (NBP2-25161B). (novusbio.com)
  • Arrestin antibody LS-C141017 is a DY550-conjugated mouse monoclonal antibody to Arrestin (SAG) from pig. (lsbio.com)
  • RAW264.7 cells were subjected to SDS PAGE followed by western blot with 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:2000 incubated at room temperature for 1.5 hours. (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human tonsil tissue slide using 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:200 (under 10x lens). (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human tonsil tissue slide using 10171-1-AP (Beta Arrestin 2 antibody) at dilution of 1:200 (under 40x lens). (ptglab.com)
  • This antibody is specific for arrestin protein. (mybiosource.com)
  • β-Arrestin 1 and 2 (Barr1 and Barr2, respectively) are intracellular signaling molecules that regulate many important metabolic functions. (jci.org)
  • β‑arrestins regulate cell proliferation, promote cell invasion and migration, transmit anti‑apoptotic survival signals and affect other characteristics of tumors, including tumor growth rate, angiogenesis, drug resistance, invasion and metastatic potential. (spandidos-publications.com)
  • Although many of these arrestin-bound effectors serve to modulate G protein signaling, degrading second messengers and regulating endocytosis and trafficking, other signals seem to extend beyond the receptor-arrestin complex to regulate such processes as protein translation and gene transcription. (aspetjournals.org)
  • We hypothesize that β-arrestins regulate oxidative stress in a Nox4-dependent manner and increase fibrosis in HF. (biologists.org)
  • In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. (diabetesjournals.org)
  • An expanded family of arrestins regulate metabolism. (semanticscholar.org)
  • Here we show that PAR4 and P2Y12 directly interact to co-regulate arrestin-2 signaling following PAR4 activation. (aspetjournals.org)
  • The potential role of arrestin in color visual processes led us to identify a cDNA encoding a cone-like arrestin in Xenopus laevis, the principle amphibian biological model system. (nih.gov)
  • To understand the regulation of melanopsin function, here we investigated the role of arrestin. (arvojournals.org)
  • The systematic arrestin name (1-4) plus the most widely used aliases for each arrestin subtype are listed in bold below: Arrestin-1 was originally identified as the S-antigen (SAG) causing uveitis (autoimmune eye disease), then independently described as a 48 kDa protein that binds light-activated phosphorylated rhodopsin before it became clear that both are one and the same. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 2016) , and of arrestin-11 complex with rhodopsin (Kang et al. (paperity.org)
  • 2017) reveal the structural basis for this competition: the C-terminus of G protein α-subunit and central "finger loop" of arrestin-1 (Figs. 1 and 2) occupy the same cavity between the cytoplasmic ends of the α-helices that opens upon activation of rhodopsin (Farrens et al. (paperity.org)
  • In mammals, arrestin-1 and arrestin-4 are largely confined to photoreceptors, whereas arrestin-2 and arrestin-3 are ubiquitous. (wikipedia.org)
  • Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. (wordnik.com)
  • Arrestin competition influences the kinetics and variability of the single-photon responses of mammalian rod photoreceptors. (semanticscholar.org)
  • 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)
  • In addition, insulin-like growth factor I receptor (IGF-IR) endocytosis is facilitated by β-arrestin-1, and internalization is necessary for IGF-I-stimulated mitogen-activated protein (MAP) kinase activation. (asm.org)
  • β‐arrestins 1 and 2 mediate clathrin‐dependent endocytosis of the β 2 AR [ 18 , 19 , 20 ]. (embopress.org)
  • Arrestins as regulatory hubs in cancer signalling pathways. (biomedsearch.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)
  • 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)
  • Understanding the signaling roles of arrestins may foster the development of pathway-selective drugs that exploit these pathways for therapeutic benefit. (aspetjournals.org)
  • Second, arrestin links the receptor to elements of the internalization machinery, clathrin and clathrin adaptor AP2, which promotes receptor internalization via coated pits and subsequent transport to internal compartments, called endosomes. (wikipedia.org)
  • G protein signaling is terminated, in large part, by arrestin binding, which uncouples the receptor and G protein and targets the receptor for internalization. (aspetjournals.org)
  • Previous studies have demonstrated that, although N -formyl peptide receptor (FPR) internalization occurs in the absence of arrestins, FPR recycling is arrestin-dependent. (pubmedcentralcanada.ca)
  • Arrestin binding sterically blocks receptor-G protein interactions, thereby terminating G protein signaling, while simultaneously providing a scaffold to coordinate the recruitment of internalization machinery, leading to receptor sequestration ( 11 - 13 ). (pubmedcentralcanada.ca)
  • Further, the inability to recruit β-arrestin was found to be associated with a reduced rate of receptor internalization and impaired chemotaxis in neutrophils. (ovid.com)
  • 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)
  • Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin. (semanticscholar.org)
  • Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, after the chromosome where its gene resides. (wikipedia.org)
  • In the HUGO database its gene is called arrestin-3. (wikipedia.org)
  • Conserved positions of multiple introns in its gene and those of our arrestin subtypes suggest that they all evolved from this ancestral arrestin. (wikipedia.org)
  • Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene. (wikipedia.org)
  • Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. (ebi.ac.uk)
  • The adaptive evolutionary relationship of Xenopus cone arrestin to the arrestin gene tree suggests high intrafamily homology and early gene duplication events. (nih.gov)
  • Unlike lengthy reporter gene assays, PathHunter ß-arrestin assays are direct and hence minimize the opportunity for off-target effects. (technologynetworks.com)
  • 8 Whereas G protein-dependent ERK translocates to the nucleus for gene transcription, arrestin-dependent ERK remains within the cytoplasm. (ahajournals.org)
  • Diesel exhaust particles activate the matrix-metalloproteinase-1 gene in human bronchial epithelia in a beta-arrestin-dependent manner via activation of RAS. (duke.edu)
  • On www.antibodies-online.com are 98 Arrestin, beta 2 (ARRB2) Antibodies from 23 different suppliers available. (antibodies-online.com)
  • We have proved that β-arrestin-1 binds to the regulatory domain of c-Raf where Ras was indentified to bind. (escholarship.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)
  • The β-arrestin recruitment assay followed by the second messenger (cAMP) assay were performed on the same cell line expressing human cholinergic muscarinic 2 (CHRM2) fused with PK. (discoverx.com)
  • Only using the β-arrestin recruitment assay (left) revealed the possible true partial agonist pharmacology for oxo-M due to the non-amplified signal nature of the β-arrestin pathway compared to the amplified G-protein dependent pathway (right). (discoverx.com)
  • In this aspect, the β-arrestin recruitment assay has added an important piece to the repertoire of assay tools in drug discovery. (discoverx.com)
  • The principle behind this guideline can be applied to all the β-arrestin assay technologies. (discoverx.com)
  • E ) A TUNEL assay revealed that apoptosis was attenuated when β-arrestin-2 was silenced. (aging-us.com)
  • Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. (ebi.ac.uk)
  • Porcine retinal S-antigen (arrestin). (lsbio.com)
  • They direct the recruitment, activation, and scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, β-arrestins 1 and 2. (sciencemag.org)
  • The functional consequences linked to a lack of β-arrestin recruitment were further explored, and we demonstrate that FPR2 desensitization occurred independent of β-arrestin. (ovid.com)
  • Since β-arrestin recruitment occurs independent of G-protein coupling, these assays provide a direct, universal platform for measuring receptor activation. (discoverx.com)
  • Our previous studies demonstrated that thrombin induces co-immunoprecipitation of PAR4 with P2Y12, together with arrestin recruitment to the complex. (aspetjournals.org)
  • Further studies revealed that recruitment of arrestin3 to the β 2 -adrenergic receptor orchestrates the sequestration of Gq-coupled receptor-induced ERK to the cytosol through direct binding of ERK to arrestin. (ahajournals.org)
  • Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. (figshare.com)
  • Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. (figshare.com)
  • 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)
  • In conjunction withbiochemical and mutagenesis data, we propose a molecular mechanism bywhich arrestin is activated for receptor binding. (embl.de)
  • Although a number of recent studies reported that β-arrestins are required for ERK1/2 activation independently of G protein coupling, molecular mechanism of β-arrestin- mediated ERK1/2 activation via c-Raf has remained unclear. (escholarship.org)
  • 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)
  • To determine whether β-adrenergic ligands that do not activate G protein signaling (i.e., β-blockers) can stabilize the β 1 AR in a signaling conformation, we screened 20 β-blockers for their ability to stimulate β-arrestin-mediated EGFR transactivation. (pnas.org)
  • The structure of the β-arrestin-1-V2Rpp-Fab30 complex shows marked conformational differences in β-arrestin-1 compared to its inactive conformation. (nature.com)
  • We describe herecrystallographic studies of visual arrestin in its basal conformation. (embl.de)
  • 17. Is Signaling Specificity Encoded in Arrestin Conformation? (ellibs.com)
  • β-arrestin (βarr) was recruited at a reduced level to CXCR3B relative to CXCR3A, which was also associated with differences in βarr2 conformation. (sigmaaldrich.com)
  • In addition, a mysterious link in functional mechanism of β-arrestin-mediated ERK1/2 activation is how c-Raf relieves autoinhibition engendering a conformation change from a closed, inactive state to an open, active state, without small GTPase Ras, which is critical for c-Raf activation in the classical G protein dependent ERK activation. (escholarship.org)
  • A synthetic peptide corresponding to C terminal residues of Human Beta Arrestin 2 (UniProt: P32121). (abcam.com)
  • The PA1-731 immunizing peptide corresponds to amino acid residues 2-18 from rat visual arrestin. (thermofisher.com)
  • The arrestin superfamily: cone arrestins are a fourth family. (ebi.ac.uk)
  • report the identification of a fungal arrestin homolog and its role in pH signaling. (sciencemag.org)
  • Thus, as with metazoan arrestin, fungal arrestin appears to contribute to 7TMR signaling, and this signaling involves similar types of posttranslational modifications as those observed for metazoan arrestin. (sciencemag.org)
  • Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. (pnas.org)
  • Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also β-arrestin-dependent signaling. (pnas.org)
  • However, hepatocyte-specific β-arrestin 2 deficiency did not affect hepatic insulin sensitivity or β-adrenergic signaling. (jci.org)
  • Importantly, hepatocyte-specific overexpression of β-arrestin 2 greatly reduced hepatic GCGR signaling and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. (jci.org)
  • Pluridimensionality of β-arrestin-dependent signaling at seven-transmembrane receptor (7TMRs). (nih.gov)
  • Some of the best-characterized β-arrestin-induced signaling mechanisms are schematically represented. (nih.gov)
  • 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)
  • 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)
  • Nonetheless, recent evidence generated using arrestin knockouts, G protein-uncoupled receptor mutants, and arrestin pathway-selective "biased agonists" is beginning to reveal that arrestin signaling plays important roles in the retina, central nervous system, cardiovascular system, bone remodeling, immune system, and cancer. (aspetjournals.org)
  • This study investigates the role of β-arrestin signaling in adult human CF isolated from normal and failing left ventricles. (ahajournals.org)
  • Inhibition of β-arrestin signaling in CF may represent a novel approach to inhibit or decrease maladaptive cardiac remodeling following myocardial injury. (ahajournals.org)
  • In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction. (diabetesjournals.org)
  • We previously reported that an upregulation of GRK2 and a decrease in β-arrestin 2 inhibit insulin-induced stimulation of Akt/eNOS signaling and that GRK2 overactivation may result from an increase in PKC activity in aortas from diabetic mice with hyperinsulinemia ( 14 ). (diabetesjournals.org)
  • PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. (aspetjournals.org)
  • 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 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)
  • 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)
  • The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intracellular Signaling of the β2-Adrenergic Receptor. (jefferson.edu)
  • 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)
  • 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)
  • W. E. Miller, S. Maudsley, S. Ahn, K. D. Khan, L. M. Luttrell, and R. J. Lefkowitz, beta-arrestin 1 interacts with the catalytic domain of the tyrosine kinase c-SRC. (springer.com)
  • This insulin-induced decrease in β-arrestin-1 content was blocked by inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) and MEK with wortmannin and PD98059, respectively. (asm.org)
  • 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)
  • 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)
  • 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)
  • S-antigen, also identified as arrestin, is a protein involved in the regulation of phototransduction. (thermofisher.com)
  • Surprisingly, several α-arrestins play prominent roles in the regulation of metabolism and obesity. (semanticscholar.org)
  • This response requires the calcium-dependent membrane-targeting C2 domain and the double SAM domain involved in AdcC oligomerization, revealing a mode of membrane targeting and regulation unique among members of the arrestin clan. (biologists.org)
  • Interestingly, β-arrestin 2 knockdown did not have this effect, demonstrating specificity for regulating TGF-β-stimulated collagen synthesis. (ahajournals.org)
  • 2017) . Structurally, arrestins are elongated two-domain molecules (Granzin et al. (paperity.org)
  • First, arrestin binding to the cytoplasmic face of the receptor occludes the binding site for heterotrimeric G-protein, preventing its activation (desensitization). (wikipedia.org)
  • 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)
  • 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)
  • 1984) . Arrestins suppress G protein activation (Wilden et al. (paperity.org)
  • S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. (genetex.com)
  • Knockdown of β-arrestin 1 and 2 using siRNA diminished the desensitization, slowing PIP 2 restoration significantly and even adding a delayed secondary phase of further PIP 2 depletion. (rupress.org)
  • 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)
  • 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)
  • 32 Arrestin 3, Retinal (X-Arrestin) (ARR3) Antikörper von 11 Herstellern verfügbar auf www.antikoerper-online.de. (antikoerper-online.de)
  • β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. (biologists.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)
  • 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)
  • PalF, a protein containing C-terminal and N-terminal arrestin domains, interacted with PalH, the 7 transmembrane receptor (7TMR) in two-hybrid assays and glutathione- S -transferase (GST) pull-down assays. (sciencemag.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intra" by Xufan Tian, Roshanak Irannejad et al. (jefferson.edu)
  • It also reveals functional redundancy between arrestins and the arrestin-like adaptors Bul1 and Bul2. (nih.gov)
  • 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)
  • Extracellular alpha-synuclein induces sphingosine S1P1R uncoupled from inhibitory G-protein leaving beta-arrestin signal intact. (antibodies-online.com)
  • 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)
  • Antiserum to human Beta arrestin-2 was raised by repeated immunisation of goats with highly purified antigen. (mybiosource.com)
  • 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)
  • 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)