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*  Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic ...
The beta-adrenergic receptor kinase is an enzyme, possibly analogous to rhodopsin kinase, that multiply phosphorylates the beta-adrenergic receptor only when it is occupied by stimulatory agonists. Since this kinase may play an important role in mediating the process of homologous, or agonist-specific, desensitization, we investigated the functional consequences of receptor phosphorylation by the kinase and possible analogies with the mechanism of action of rhodopsin kinase. Pure hamster lung beta 2-adrenergic receptor, reconstituted in phospholipid vesicles, was assessed for its ability to mediate agonist-promoted stimulation of the GTPase activity of ...
  https://dukespace.lib.duke.edu/dspace/handle/10161/7874
*  "G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabo" by Jianjun Wang, Jiansong Luo et al.
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive grk-2 or by the selective expression of grk-2 in hermaphrodite-specific neurons. The addition of 5-HT or inhibition of 5-HT metabolism also rescued the egg laying defect. Furthermore, we demonstrate that AMX-2 is the primary monoamine oxidase that metabolizes 5-HT in C. elegans, and we also found that grk-2 loss-of-function strains have ...
  http://jdc.jefferson.edu/bmpfp/117/
*  What does g-protein-coupled receptor kinase 2 mean?
Looking for the meaning of g-protein-coupled receptor kinase 2? Find out what is the meaning of g-protein-coupled receptor kinase 2 on Phrases.net! The Web's largest and most authoritative phrases and idioms resource.
  http://www.phrases.net/psearch/g-protein-coupled%20receptor%20kinase%202
*  G Protein-Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane...
Our data demonstrate the novel finding that GRK5 activity attenuates atherosclerosis, and that it does so through distinct antiatherogenic mechanisms in ECs, SMCs, monocytes, and Mϕs. These cell-specific mechanisms encompass diverse signaling systems, including the receptor tyrosine kinases CSF-1R and PDGFRβ, the 7-transmembrane receptor CCR2, the innate immunity receptors TLR4 and TNFR1, and the transcription factor NF-κB. Thus, despite data from overexpression and model cell systems suggesting the possibility that GRK5 could mediate proatherogenic activities,9,11,13,14 net physiological GRK5 activity clearly appears to be antiatherogenic.. Because GRK5-mediated phosphorylation of 7-transmembrane receptors promotes receptor/β-arrestin association,1 it may seem paradoxical that whereas GRK5 activity is antiatherogenic, β-arrestin2 activity is proatherogenic.19 However, at least 2 possibilities may help ...
  http://atvb.ahajournals.org/content/32/2/308
*  DIGITAL.CSIC: G protein-coupled receptor kinase 2 plays a role in the development of non-alcoholic steatohepatitis
Introduction]: Insulin resistance (IR) and obesity are major health problems and important risk factors for the development of non-alcoholic fatty liver disease, a disease spectrum that may include hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. G protein-coupled receptor kinase 2 (GRK2), first identified as a regulator of G protein-coupled receptors (GPCRs), has been described to play a relevant role in the development of IR and obesity in vivo. However, the effect of GRK2 in the development of NASH had not been addressed so far. Since the deletion of GRK2 prevents excessive body weight gain, we fed WT and GRK2 global hemizygous mice (GRK2+/-) with a methionine and choline-deficient diet (MCD), a well stablished model of NASH that is independent of fat mass accretion. [Results]: Even though the MCD diet induced similar metabolic alterations and a comparable elevation in plasma transaminase activity in WT and GRK2+/- mice, ...
  http://digital.csic.es/handle/10261/154193
*  G-protein-coupled receptor kinases and the heart. - Semantic Scholar
The family of G-protein-coupled receptors includes many well-studied members, such as the adrenergic and the muscarinic acetylcholine receptors. These receptors are regulated by multiple mechanisms that serve to adapt their expression and their function to a rapidly changing environment. One of the most intriguing and important regulatory mechanisms involves the phosphorylation of such receptors by a set of specific kinases, termed the G-protein-coupled receptor kinases (GRKs). This phosphorylation is followed by binding of specific arrestin proteins to the phosphorylated receptors, which uncouples the receptors from their G proteins and thus causes a loss of receptor function. Several isoforms of the GRKs and the arrestins are expressed in the heart. They may be involved in the loss of ...
  https://www.semanticscholar.org/paper/G-protein-coupled-receptor-kinases-and-the-heart-Lohse/c44fd78ee43b678dc316112f17eb71a7d3e39e1f
*  Abstract 479: A novel Interaction Between G protein-Coupled Receptor Kinase 4 and Sorting Nexin 5 in the Regulation of Dopamine...
A dysfunction of the renal dopaminergic system is implicated in the pathogenesis of essential hypertension. Independent of renal nerves, the kidney synthesizes dopamine to regulate salt and water homeostasis by inhibiting ion transport in the nephron. The dopamine D1 receptor (D1R) plays a pivotal role in regulating salt metabolism and blood pressure. The regulatory mechanisms or proteins involved in D1R trafficking are not completely understood, although our group has reported how G protein-coupled receptor kinase 4 (GRK4) promotes agonist-activated D1R desensitization and plasma membrane localization. We have recently identified the sorting nexin 5 (SNX5)_a protein involved in protein trafficking and a member of the mammalian retromer_as a novel binding partner of D1R using a yeast two-hybrid screen and have endeavored to elucidate how GRK4 and SNX5 cooperatively interact and regulate the D1R. Using a series of biological, biophysical and immunological ...
  http://hyper.ahajournals.org/content/60/Suppl_1/A479
*  Wu, C.C., Tsai, F.M., Shyu, R.Y., Tsai, Y.M., Wang, C.H. and Jiang, S.Y. (2011) G protein-coupled receptor kinase 5 mediates...
Wu, C.C., Tsai, F.M., Shyu, R.Y., Tsai, Y.M., Wang, C.H. and Jiang, S.Y. (2011) G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells. BMC Cancer, 11, 175.
  http://www.scirp.org/reference/ReferencesPapers.aspx?ReferenceID=1022632
*  G-Protein-Coupled Receptor Kinases Summary Report | CureHunter
G-Protein-Coupled Receptor Kinases: 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.
  http://www.curehunter.com/public/keywordSummaryD054768-G-Protein-Coupled-Receptor-Kinases.do
*  Transgenic mice targeting the heart unveil G protein-coupled receptor kinases as therapeutic targets. | Archivio della ricerca...
GRKs critically regulate betaAR signaling via receptor phosphorylation and the triggering of desensitization. In the heart, betaARs control the chronotropic, lusitropic, and inotropic responses to the catecholamine neurotransmitters, norepinephrine and epinephrine. Signaling through cardiac betaARs is significantly impaired in many cardiovascular disorders, including congestive heart failure. betaARK1 (also known as GRK2) is the most abundant GRK in the heart, and it is increased in several cardiovascular diseases associated with impaired cardiac signaling and function, suggesting that this molecule could have pathophysiological relevance in the setting of heart failure. The ability to manipulate the mouse genome has provided a powerful tool to study the physiological implications of altering GRK activity and expression in the heart. Recent studies in ...
  https://www.iris.unisa.it/handle/11386/3023593
*  Abstract 15514: Lymphoid but Not Phagocytic Deficiency in G Protein-Coupled Receptor Kinase 2 Decreases Atherosclerotic Plaque...
Background: Migration of leukocytes towards sites of inflammation, such as atherosclerotic lesions, is guided through chemokines, which interact with G protein-coupled receptors (GPCR) on leukocytes. This process is controlled by phosphorylation of these receptors through GPCR kinases (GRK). GRKs dampen the response of the chemokine signaling and as such regulate the migration of leukocytes towards the lesion. Given the major role of CCR1, CCR2, and CCR5 in atherogenesis, we focussed on GRK2 in this study, and assessed the role of GRK2 deficiency in haematopoietic cells on the atherogenic response in LDLr−/− mice.. Methods & Results: A bone marrow transplant was performed to generate LDLr−/− chimeras with a partial GRK2 deficiency in the haematopoietic lineage. GRK2+/− chimeras developed smaller lesions compared with wild-type controls (WT 585.0 ± 56.4x103 μm2 vs GRK2+/− 403.0 ± 43.8x103 μm2; p=0.017). Moreover, lesions in the GRK2+/− mice also had a 78% ...
  http://circ.ahajournals.org/content/122/Suppl_21/A15514
*  Grk2 - Beta-adrenergic receptor kinase 1 - Mus musculus (Mouse) - Grk2 gene & protein
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
  http://www.uniprot.org/uniprot/F6Y9P3
*  Zhao P et al. (2015), Neutrophil Elastase Activates Protease-activate... - Xenbase Paper
Proteases that cleave protease-activated receptor-2 (PAR(2)) at Arg(36)↓Ser(37) reveal a tethered ligand that binds to the cleaved receptor. PAR(2) activates transient receptor potential (TRP) channels of nociceptive neurons to induce neurogenic inflammation and pain. Although proteases that cleave PAR(2) at non-canonical sites can trigger distinct signaling cascades, the functional importance of the PAR(2)-biased agonism is uncertain. We investigated whether neutrophil elastase, a biased agonist of PAR(2), causes inflammation and pain by activating PAR2 and TRP vanilloid 4 (TRPV4). Elastase cleaved human PAR(2) at Ala(66)↓Ser(67) and Ser(67)↓Val(68). Elastase stimulated PAR(2)-dependent cAMP accumulation and ERK1/2 activation, but not Ca(2+) mobilization, in KNRK cells. Elastase induced PAR(2) coupling to Gαs but not Gαq in HEK293 cells. Although elastase did not promote recruitment of G protein-coupled receptor kinase-2 ...
  http://www.xenbase.org/literature/article.do?method=display&articleId=50599
*  Vascular Smooth Muscle Overexpression of G Protein-Coupled Receptor Kinase 5 Elevates Blood Pressure, Which Segregates With Sex...
Thank you for your interest in spreading the word on Circulation.. 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. ...
  http://circ.ahajournals.org/content/early/2005/08/15/CIRCULATIONAHA.104.531657
*  G protein-coupled receptor kinase Protein Superfamily Detail
MGI protein superfamily detail pages represent the protein classification set for a homeomorphic superfamily from the Protein Information Resource SuperFamily (PIRSF) site.. Mouse superfamily members are shown with links to their corresponding HomoloGene Classes. Note that pseudogenes are included in PIRSF families but not in orthology sets used here. You can select a given mouse superfamily member and download (or forward to NCBI BLAST) FASTA formatted protein sequences of that mouse gene and its mouse, human and rat homologs, as defined in the corresponding HomoloGene Class. The numbers of mouse, human and rat genes in the HomoloGene Class are shown. You can also "Select all" mouse superfamily members to obtain their protein sequences and the protein sequences for all mouse, human and rat homologs of the mouse superfamily members.. The number of protein sequences returned does not always match the numbers of homologs shown, because the same protein sequence can be associated with multiple ...
  http://www.informatics.jax.org/vocab/pirsf/PIRSF000584
*  Ad-GIT2 [SL100903] - $618.00 : SignaGen Laboratories, A Gene Delivery Company Providing Custom AAV Adenovirus Lentivirus...
SignaGen Laboratories, A Gene Delivery Company Providing Custom AAV Adenovirus Lentivirus Production Services & Manufacturing DNA/siRNA Transfection Reagents... Ad-GIT2 [SL100903] - Product Category: Human Adenovirus Type5 (dE1/E3) expressing G Protein-coupled Receptor Kinase Interactor 2 (GIT2) under a CMV promoter. Product Information Product Name: G Protein-coupled Receptor Kinase Interactor 2, pre-packaged adenovirus, ready to ship and ready to use format. Promoter: CMV Titer: 1E+10~1E+11 PFU/ml Storage Buffer: DMEM with 2.5% BSA, 2.5% glycerol Gene Information Gene Name: G
  http://signagen.com/index.php?main_page=product_info&cPath=140&products_id=48124
*  Abstract 1303: GRK2ct Expression in Vascular Smooth Muscle (VSM) Potentates β-Adrenergic Receptor (AR) Mediated Relaxation |...
Introduction: Elevated levels of G protein-coupled receptor kinase 2 (GRK2) are associated with human hypertension and animal models of the disease. GRK2 is also increased in heart failure (HF). GRK2ct, a peptide inhibitor of GRK2 (last 194 amino acids of GRK2) is effective at rescuing models of HF through its restoration of cardiac βAR signaling.. Hypothesis: Our interest is in investigating the role of VSM GRK2ct to determine if it is an effective antihypertensive strategy.. Methods: We created transgenic mice that express the GRK2ct peptide in VSM using a portion of the SM22 promoter (VSM-GRK2ct). Conscious BP was derived using a fluid-filled indwelling left common carotid artery catheter. In vivo BP response to acute agonist infusion administered via the jugular vein was recorded in anesthetized mice. Vascular reactivity was determined by force displacement in aortic rings after mechanical endothelial cell denudation.. Results: RNA and protein levels verified ...
  http://circ.ahajournals.org/content/114/Suppl_18/II_246.4
*  GRK4 Gene - GeneCards | GRK4 Protein | GRK4 Antibody
Complete information for GRK4 gene (Protein Coding), G Protein-Coupled Receptor Kinase 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
  http://www.genecards.org/cgi-bin/carddisp.pl?gene=GRK4&keywords=GH04G002946&prefilter=genomic_location
*  GRK4 Gene - GeneCards | GRK4 Protein | GRK4 Antibody
Complete information for GRK4 gene (Protein Coding), G Protein-Coupled Receptor Kinase 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
  http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=2868
*  Robert J. Lefkowitz | Duke Chemistry
Current projects emphasize attempts to understand regulation of the receptors and their desensitization which occurs in response to persistent stimulation. We are isolating the enzymes and proteins involved in these processes and studying their mechanisms of action in isolated protein and cellular systems as well as in whole animals. Most important are special enzymes called G protein-coupled receptor kinases which phosphorylate the receptors and lead to their desensitization which occurs when they bind a second protein called barrestin. Most recently we have been developing lines of transgenic animals in which these various proteins are either overexpressed or "knockedout" by homologous recombination. These genetically altered animal lines are helping to shed new light on the ways in which receptors are regulated. They also have suggested several novel approaches to human therapeutics ...
  http://chem.duke.edu/faculty/robert-j-lefkowitz?page=10
*  Robert J. Lefkowitz | Duke Chemistry
Current projects emphasize attempts to understand regulation of the receptors and their desensitization which occurs in response to persistent stimulation. We are isolating the enzymes and proteins involved in these processes and studying their mechanisms of action in isolated protein and cellular systems as well as in whole animals. Most important are special enzymes called G protein-coupled receptor kinases which phosphorylate the receptors and lead to their desensitization which occurs when they bind a second protein called barrestin. Most recently we have been developing lines of transgenic animals in which these various proteins are either overexpressed or "knockedout" by homologous recombination. These genetically altered animal lines are helping to shed new light on the ways in which receptors are regulated. They also have suggested several novel approaches to human therapeutics ...
  http://chem.duke.edu/faculty/robert-j-lefkowitz?page=12
*  Toxicology and Cancer Biology
G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila ...
  http://toxicology.med.uky.edu/node?page=6
*  Plus it
Activator of G-protein signaling 4 (AGS4)/G-protein signaling modulator 3 (Gpsm3) contains three G-protein regulatory (GPR) motifs, each of which can bind Gαi-GDP free of Gβγ. We previously demonstrated that the AGS4-Gαi interaction is regulated by seven transmembrane-spanning receptors (7-TMR), which may reflect direct coupling of the GPR-Gαi module to the receptor analogous to canonical Gαβγ heterotrimer. Here, we demonstrate that the AGS4-Gαi complex is regulated by chemokine receptors in an agonist-dependent manner that is receptor-proximal. As an initial approach to investigate the functional role(s) of this regulated interaction in vivo, we analyzed leukocytes, in which AGS4/Gpsm3 is predominantly expressed, from AGS4/Gpsm3-null mice. Loss of AGS4/Gpsm3 resulted in a mild but significant neutropenia and leukocytosis. Dendritic cells, T lymphocytes and neutrophils from AGS4/Gpsm3-null mice also exhibited significant defects in ...
  http://jpet.aspetjournals.org/content/early/2017/01/06/jpet.116.238436
*  Plus it
The mechanisms of desensitization and resensitization of the dopamine D1 receptor are not well understood. Although the high homology of the D1 receptor with the β2-adrenergic receptor might indicate that similar mechanisms regulate the responsiveness of the receptors, even subtypes of β-adrenergic receptors differ substantially in this respect (Shiina et al., 2000). For β-adrenergic receptors, a distinction has been made between desensitization that is homologous (resulting from stimulation of the same receptor) or heterologous (resulting from stimulation of a different receptor subtype, or nonreceptor-mediated activation of a second messenger) (Harden, 1983). A mechanism for heterologous desensitization is phosphorylation of the receptor ...
  http://molpharm.aspetjournals.org/content/61/4/806
*  Cardiac Function in Mice Overexpressing the β-Adrenergic Receptor Kinase or a βARK Inhibitor | Circulation
Thank you for your interest in spreading the word on Circulation.. 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. ...
  http://circ.ahajournals.org/content/92/3/277