October 2017 ~. The Florida Office of Insurance Regulation (FLOIR) has announced the submission of proposed rates for 2018 Federal Patient Protection & Affordable Care Act (PPACA) health insurance plans.. According to the press release, rates for individual major medical plans which comply with the coverage requirements of PPACA may increase an average of 44.7% at the start of next year. 31% of which will be allotted to Silver plans offered on the Exchange.. The FLOIR states that most consumers with the Silver plans will not experience and increase in out-of-pocket costs, as the federal premium subsidy will also increase to absorb this extra cost, and could potentially see a slight decrease in out-of-pocket health insurance premiums in 2018.. Consumers enrolled in a Silver on-Exchange plan that do not receive a premium subsidy will have the option of purchasing a similar off-Exchange Silver plan without this extra cost, according to the release. Plans other than the on-Exchange Silver plans will ...
Previous work from our laboratory indicates that the dopamine D2 receptor (D2R) in the kidney has a direct role in regulating renal inflammation and injury and blood pressure. Some common single nucleotide polymorphisms (D2R SNPs; rs 6276, 6277, and 1800497) in the human DRD2 gene are associated with decreased D2R expression and function. Immortalized renal proximal tubule cells (RPTCs) from subjects carrying D2R SNPs (RPTC-D2R SNPs) express less D2Rs than RPTCs carrying no D2R SNPs (RPTC-D2R WT) (62±4 vs 100±6%; P,0.04) and a pro-inflammatory and pro-fibrotic phenotype with markers of epithelial mesenchymal transition. RPTC-D2R SNPs showed increased apoptosis compared with RPTC-D2R WT (11± 0.8 vs 2.3±0.4% TUNEL positive cells, P,0.01, n=5/group). We hypothesized that the D2R regulates renal cell survival through effects on Wnt signaling. We found that Wnt3 expression was increased in RPTC-D2R SNPs compared with RPTC-D2R WT (mRNA: 2.6±0.35 vs 1±0.11 fold; P,0.05; protein: 133±4 vs ...
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.
Fingerprint Dive into the research topics of Nuclear Translocation of Cardiac G Protein-Coupled Receptor Kinase 5 Downstream of Select Gq-Activating Hypertrophic Ligands Is a Calmodulin-Dependent Process. Together they form a unique fingerprint. ...
Looking for online definition of homologous desensitization in the Medical Dictionary? homologous desensitization explanation free. What is homologous desensitization? Meaning of homologous desensitization medical term. What does homologous desensitization mean?
The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activi …
Transcript Variant: This variant (7) has multiple differences compared to variant 1. These differences result in a distinct 5 UTR, 3 UTR, and 3 coding region, and cause translation initiation from a downstream start codon. The encoded isoform (g) has a shorter N-terminus and a distinct and shorter C-terminus, compared to isoform a ...
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
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 receptor function in response to drugs. Furthermore, increased expression of one of the GRKs, β-adrenergic receptor kinase-1, has been found in failing hearts, and its increased activity may contribute to the loss of β
This study was initiated by revealing that two phases of dose-dependent Aβ effects existed in cultured microglial cells. One phase involves Aβ, in the micromolar range, directly inducing microglial TNF-α release as demonstrated previously (Meda et al., 1995). In addition to this known effect produced directly by Aβ, we discovered that, in the subthreshold nanomolar range, soluble Aβ, although insufficient to directly induce TNF-α release, can potentiate, in a dose-dependent manner, TNF-α release induced by other microglial activators, preferentially those that do so via GPCRs. Microglia-mediated inflammation is an important component of AD pathology (McGeer and McGeer, 2001). We showed recently that the ultimate coagulation factor, thrombin, a serine protease with elevated levels in AD brains (Akiyama et al., 1992), can activate microglial cells (as demonstrated by TNF-α induction, inducible nitric oxide synthase, and CD40 upregulation, etc.) via activation of G-protein-coupled PARs (Suo ...
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GRK6 - GRK6 (untagged)-Kinase deficient mutant (K215M) of Human G protein-coupled receptor kinase 6 (GRK6), transcript variant 2 available for purchase from OriGene - Your Gene Company.
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The metabotropic glutamate 1 (mGlu(1)) receptor in cerebellar Purkinje cells plays a key role in motor learning and motor coordination. Here we show that the G protein-coupled receptor kinases (GRK) 2 and 4, which are expressed in these cells, regulate the mGlu(1) receptor by at least in part different mechanisms. Using kinase-dead mutants in HEK293 cells, we found that GRK4, but not GRK2, needs the intact kinase activity to desensitize the mGlu(1) receptor, whereas GRK2, but not GRK4, can interact with and regulate directly the activated Galpha(q). In cells transfected with GRK4 and exposed to agonist, beta-arrestin was first recruited to plasma membranes, where it was co-localized with the mGlu(1) receptor, and then internalized in vesicles. The receptor was also internalized but in different vesicles. The expression of beta-arrestin V53D dominant negative mutant, which did not affect the mGlu(1) receptor internalization, reduced by 70-80% the stimulation of mitogen-activated protein (MAP) ...
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7. Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK7 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK7, also called iodopsin kinase, belongs to the visual group of GRKs. It is primarily ...
The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a ...
The major finding of this study is that GIT1 is an important regulator of vascular remodeling. Specifically, we found that GIT1 depletion inhibited intima formation after carotid ligation by 50%. In vivo and in vitro analysis showed a key role for GIT1 in VSMC proliferation, migration, and apoptosis during vascular remodeling (Figure III in the online-only Data Supplement). Furthermore, GIT1 is required for VSMC proliferation through PLCγ and ERK1/2 by regulating the expression of cell cycle-related proteins, such as cyclin D1. GIT1 is also essential for cell survival by regulating VSMC apoptosis through PLCγ and cell migration through PLCγ and ERK1/2.. VSMC proliferation and migration are key components in vascular remodeling.1,2 The present study shows that GIT1 expression is highly regulated by AngII and PDGF in vitro, and during vascular remodeling in vivo. The role of GIT1 in mediating VSMC proliferation was demonstrated by several assays, including in vitro cell count, [3H]-thymidine ...
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% reduction in necrotic ...
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TY - JOUR. T1 - Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2. AU - Chen, Jing Yu. AU - Wu, Hua Xun. AU - Chen, Yin. AU - Zhang, Ling Ling. AU - Wang, Qingtong. AU - Sun, Wu Yi. AU - Wei, Wei. PY - 2012/3/13. Y1 - 2012/3/13. N2 - Paeoniflorin (Pae) is a monoterpene glucoside and the main component of the total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora. Its anti-inflammatory effect is associated with regulating G-protein-coupled receptors (GPCRs) signaling. The aim of this study was to explore the expression change of G-protein-coupled receptor kinase 2 (GRK2) in fibroblast-like synoviocytes (FLS) and the effect of Pae. Pae was obtained and purified from the roots of Paeonia lactiflora. We investigated the expression of GRK2 in synovium during the inflammatory process and assessed the effects of a specific GRK2 inhibitor and Pae on proliferation, cAMP level, and protein kinase A (PKA) ...
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3. Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK3 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK3 (also known as beta-adrenergic receptor kinase 2) is widely expressed in many ...
Next-day shipping cDNA ORF clones derived from GRK2 G protein-coupled receptor kinase 2 available at GenScript, starting from $99.00.
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 ...
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 ...
GIT2 - GIT2 (Myc-DDK-tagged)-Human G protein-coupled receptor kinase interacting ArfGAP 2 (GIT2), transcript variant 6 available for purchase from OriGene - Your Gene Company.
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 ...
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, other negative effects of the MCD were ...
The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the ...
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