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https://www.readbyqxmd.com/read/27792639/downregulation-of-renal-g-protein-coupled-receptor-kinase-type-4-expression-via-ultrasound-targeted-microbubble-destruction-lowers-blood-pressure-in-spontaneously-hypertensive-rats
#1
Hefei Huang, Xiaolong Li, Shuo Zheng, Yue Chen, Caiyu Chen, Jialiang Wang, Haipeng Tong, Lin Zhou, Jian Yang, Chunyu Zeng
BACKGROUND: G protein-coupled receptor kinase type 4 (GRK4) plays a vital role in the long-term control of blood pressure (BP) and sodium excretion by regulating renal G protein-coupled receptor phosphorylation, including dopamine type 1 receptor (D1R). Ultrasound-targeted microbubble destruction (UTMD) is a promising method for gene delivery. Whether this method can deliver GRK4 small interfering RNA (siRNA) and lower BP is not known. METHODS AND RESULTS: BP, 24-hour sodium excretion, and urine volume were measured after UTMD-targeted GRK4 siRNA delivery to the kidney in spontaneously hypertensive rats...
October 6, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27677134/role-of-grk4-in-the-regulation-of-arterial-at1-receptor-in-hypertension
#2
K Chen, C Fu, C Chen, P A Jose, C Zeng
No abstract text is available yet for this article.
July 2016: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/26820533/inhibitory-effects-of-two-g-protein-coupled-receptor-kinases-on-the-cell-surface-expression-and-signaling-of-the-human-adrenomedullin-receptor
#3
Kenji Kuwasako, Toshio Sekiguchi, Sayaka Nagata, Danfeng Jiang, Hidetaka Hayashi, Manabu Murakami, Yuichi Hattori, Kazuo Kitamura, Johji Kato
Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM1 receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM1 receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM1 receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [(125)I]AM binding and AM-induced cAMP production...
February 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26250109/the-fmrp-grk4-mrna-interaction-uncovers-a-new-mode-of-binding-of-the-fragile-x-mental-retardation-protein-in-cerebellum
#4
Thomas Maurin, Mireille Melko, Sabiha Abekhoukh, Olfa Khalfallah, Laetitia Davidovic, Marielle Jarjat, Simona D'Antoni, Maria Vincenza Catania, Hervé Moine, Elias Bechara, Barbara Bardoni
Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is caused by the silencing of the FMR1 gene encoding an RNA-binding protein (FMRP) mainly involved in translational control. We characterized the interaction between FMRP and the mRNA of GRK4, a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase super-family, both in vitro and in vivo. While the mRNA level of GRK4 is unchanged in the absence or in the presence of FMRP in different regions of the brain, GRK4 protein level is increased in Fmr1-null cerebellum, suggesting that FMRP negatively modulates the expression of GRK4 at the translational level in this brain region...
September 30, 2015: Nucleic Acids Research
https://www.readbyqxmd.com/read/26134571/structure-and-function-of-the-hypertension-variant-a486v-of-g-protein-coupled-receptor-kinase-4
#5
Samantha J Allen, Gopal Parthasarathy, Paul L Darke, Ronald E Diehl, Rachael E Ford, Dawn L Hall, Scott A Johnson, John C Reid, Keith W Rickert, Jennifer M Shipman, Stephen M Soisson, Paul Zuck, Sanjeev K Munshi, Kevin J Lumb
G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the process of GPCR desensitization and internalization. GRK4 is implicated in the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associated with hypertension. Here, we describe the 2.6 Å structure of human GRK4α A486V crystallized in the presence of 5'-adenylyl β,γ-imidodiphosphate. The structure of GRK4α is similar to other GRKs, although slight differences exist within the RGS homology (RH) bundle subdomain, substrate-binding site, and kinase C-tail...
August 14, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25857252/%C3%AE-1-adrenoceptor-activation-of-pkc-%C3%AE%C2%B5-causes-heterologous-desensitization-of-thromboxane-receptors-in-the-aorta-of-spontaneously-hypertensive-rats
#6
Yingzi Zhao, Paul M Vanhoutte, Susan W S Leung
BACKGROUND AND PURPOSE: In the aorta of adult spontaneously hypertensive (SHR), but not in that of normotensive Wistar-Kyoto (WKY), rats, previous exposure to phenylephrine inhibits subsequent contractions to PGE2 . The present experiments were designed to examine the mechanism(s) underlying this inhibition. EXPERIMENTAL APPROACH: Isometric tension was measured in isolated rings of SHR and WKY aortae. Gene expression and protein presence were measured by quantitative real-time PCR and Western blotting respectively...
July 2015: British Journal of Pharmacology
https://www.readbyqxmd.com/read/25775155/the-importance-of-g-protein-coupled-receptor-kinase-4-grk4-in-pathogenesis-of-salt-sensitivity-salt-sensitive-hypertension-and-response-to-antihypertensive-treatment
#7
REVIEW
Brian Rayner, Raj Ramesar
Salt sensitivity is probably caused by either a hereditary or acquired defect of salt excretion by the kidney, and it is reasonable to consider that this is the basis for differences in hypertension between black and white people. Dopamine acts in an autocrine/paracrine fashion to promote natriuresis in the proximal tubule and thick ascending loop of Henle. G-protein receptor kinases (or GRKs) are serine and threonine kinases that phosphorylate G protein-coupled receptors in response to agonist stimulation and uncouple the dopamine receptor from its G protein...
2015: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/25770216/g-protein-coupled-receptor-kinases-of-the-grk4-protein-subfamily-phosphorylate-inactive-g-protein-coupled-receptors-gpcrs
#8
Lingyong Li, Kristoff T Homan, Sergey A Vishnivetskiy, Aashish Manglik, John J G Tesmer, Vsevolod V Gurevich, Eugenia V Gurevich
G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of GPCRs. It is widely assumed that most GRKs selectively phosphorylate only active GPCRs. Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors, which are commonly used as representative models for GPCRs. Agonist-independent GPCR phosphorylation cannot be explained by constitutive activity of the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6...
April 24, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25768006/gender-based-differences-on-the-association-between-salt-sensitive-genes-and-obesity-in-korean-children-aged-between-8-and-9-years
#9
Myoungsook Lee, Mi Kyung Kim, Seon-Mee Kim, Hyesoon Park, Chang Gyu Park, Hye Kyung Park
BACKGROUND: High sodium intake is associated with the development of chronic diseases such as obesity. Although its role in obesity remains controversial, there may be a correlation between salt sensitivity and the early onset of chronic diseases in obese children. METHODS: In all, 2,163 Korean children (1,106 boys and 1,057 girls) aged 8-9 years were recruited from seven elementary schools in Seoul. To evaluate whether obesity risk was modulated by the salt sensitivity, 11 SNPs related to salt sensitive genes (SSG) became the target of sodium intakes in obese children...
2015: PloS One
https://www.readbyqxmd.com/read/25732908/common-variants-of-the-g-protein-coupled-receptor-type-4-are-associated-with-human-essential-hypertension-and-predict-the-blood-pressure-response-to-angiotensin-receptor-blockade
#10
H Sanada, M Yoneda, J Yatabe, S M Williams, J Bartlett, M J White, L N Gordon, R A Felder, G M Eisner, I Armando, P A Jose
Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4(142V), with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693)...
February 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/25236748/prenatal-lipopolysaccharide-exposure-results-in-dysfunction-of-the-renal-dopamine-d1-receptor-in-offspring
#11
Xinquan Wang, Hao Luo, Caiyu Chen, Ken Chen, Jialiang Wang, Yue Cai, Shuo Zheng, Xiaoli Yang, Lin Zhou, Pedro A Jose, Chunyu Zeng
Adverse environment in early life can modulate the adult phenotype, including blood pressure. Lipopolysaccharide (LPS) exposure in utero results in increased blood pressure in the offspring, but the exact mechanisms are not clear. Studies have shown that the renal dopamine D1 receptor (D1R) plays an important role in maintaining sodium homeostasis and normal blood pressure; dysfunction of D1R is associated with oxidative stress and hypertension. In this study, we determined if dysfunction of the renal D1R is involved in fetal-programmed hypertension, and if oxidative stress contributes to this process...
November 2014: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/25150869/g-protein-coupled-receptor-accessory-proteins-and-signaling-pharmacogenomic-insights
#12
REVIEW
Miles D Thompson, David E C Cole, Pedro A Jose, Peter Chidiac
The identification and characterization of the genes encoding G protein-coupled receptors (GPCRs) and the proteins necessary for the processes of ligand binding, GPCR activation, inactivation, and receptor trafficking to the membrane are discussed in the context of human genetic disease. In addition to functional GPCR variants, the identification of genetic disruptions affecting proteins necessary to GPCR functions have provided insights into the function of these pathways. Gsα and Gβ subunit polymorphisms have been found to result in complex phenotypes...
2014: Methods in Molecular Biology
https://www.readbyqxmd.com/read/25134060/the-renal-dopaminergic-system-novel-diagnostic-and-therapeutic-approaches-in-hypertension-and-kidney-disease
#13
REVIEW
Ines Armando, Prasad Konkalmatt, Robin A Felder, Pedro A Jose
Salt sensitivity of blood pressure, whether in hypertensive or normotensive subjects, is associated with increased cardiovascular risk and overall mortality. Salt sensitivity can be treated by reducing NaCl consumption. However, decreasing salt intake in some may actually increase cardiovascular risk, including an increase in blood pressure, that is, inverse salt sensitivity. Several genes have been associated with salt sensitivity and inverse salt sensitivity. Some of these genes encode proteins expressed in the kidney that are needed to excrete a sodium load, for example, dopamine receptors and their regulators, G protein-coupled receptor kinase 4 (GRK4)...
April 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/25023003/novel-candidate-genes-putatively-involved-in-stress-fracture-predisposition-detected-by-whole-exome-sequencing
#14
Eitan Friedman, Daniel S Moran, Danny Ben-Avraham, Ran Yanovich, Gil Atzmon
While genetic factors in all likelihood contribute to stress fracture (SF) pathogenesis, a few studies focusing on candidate genes have previously been reported. The objective of this study is to gain better understanding on the genetic basis of SF in a gene-naive manner. Exome sequence capture followed by massive parallel sequencing of two pooled DNA samples from Israeli combat soldiers was employed: cases with high grade SF and ethnically matched healthy controls. The resulting sequence variants were individually verified using the Sequenom™ platform and the contribution of the genetic alterations was validated in a second cohort of cases and controls...
2014: Genetics Research
https://www.readbyqxmd.com/read/24807909/the-regulator-of-g-protein-signaling-rgs-domain-of-g-protein-coupled-receptor-kinase-5-grk5-regulates-plasma-membrane-localization-and-function
#15
Hua Xu, Xiaoshan Jiang, Ke Shen, Christopher C Fischer, Philip B Wedegaertner
The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs at the plasma membrane (PM). Here GRK5/GRK4 chimeras and point mutations in GRK5 identify a short sequence within the regulator of G protein signaling (RGS) domain in GRK5 that is critical for GRK5 PM localization. This region of the RGS domain of GRK5 coincides with a region of GRK6 and GRK1 shown to form a hydrophobic dimeric interface (HDI) in crystal structures. Coimmunoprecipitation (coIP) and acceptor photobleaching fluorescence resonance energy transfer assays show that expressed GRK5 self-associates in cells, whereas GRK5-M165E/F166E (GRK5-EE), containing hydrophilic mutations in the HDI region of the RGS domain, displays greatly decreased coIP interactions...
July 1, 2014: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/24658007/variation-in-genes-that-regulate-blood-pressure-are-associated-with-glomerular-filtration-rate-in-chinese
#16
May E Montasser, Lawrence C Shimmin, Dongfeng Gu, Jing Chen, Charles Gu, Tanika N Kelly, Cashell E Jaquish, Treva K Rice, Dabeeru C Rao, Jie Cao, Jichun Chen, De-PeLiu, Paul K Whelton, Lotuce Lee Hamm, Jiang He, James E Hixson
Chronic kidney disease (CKD) can be a consequence of diabetes, hypertension, immunologic disorders, and other exposures, as well as genetic factors that are still largely unknown. Glomerular filtration rate (GFR), which is widely used to measure kidney function, has a heritability ranging from 25% to 75%, but only 1.5% of this heritability is explained by genetic loci that have been identified to date. In this study we tested for associations between GFR and 234 SNPs in 26 genes from pathways of blood pressure regulation in 3,025 rural Chinese participants of the "Genetic Epidemiology Network of Salt Sensitivity" (GenSalt) study...
2014: PloS One
https://www.readbyqxmd.com/read/24597858/multiple-functions-of-g-protein-coupled-receptor-kinases
#17
Kenji Watari, Michio Nakaya, Hitoshi Kurose
Desensitization is a physiological feedback mechanism that blocks detrimental effects of persistent stimulation. G protein-coupled receptor kinase 2 (GRK2) was originally identified as the kinase that mediates G protein-coupled receptor (GPCR) desensitization. Subsequent studies revealed that GRK is a family composed of seven isoforms (GRK1-GRK7). Each GRK shows a differential expression pattern. GRK1, GRK4, and GRK7 are expressed in limited tissues. In contrast, GRK2, GRK3, GRK5, and GRK6 are ubiquitously expressed throughout the body...
2014: Journal of Molecular Signaling
https://www.readbyqxmd.com/read/24218433/role-of-grk4-in-the-regulation-of-arterial-at1-receptor-in-hypertension
#18
Ken Chen, Chunjiang Fu, Caiyu Chen, Li Liu, Hongmei Ren, Yu Han, Jian Yang, Duofen He, Lin Zhou, Zhiwei Yang, Lianfeng Zhang, Pedro A Jose, Chunyu Zeng
G-protein-coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin-angiotensin system functions, cause sodium retention and increase blood pressure. Whether GRK4 and the angiotensin type 1 receptor (AT(1)R) interact in the aorta is not known. We report that GRK4 is expressed in vascular smooth muscle cells of the aorta. Heterologous expression of the GRK4γ variant 142V in A10 cells increased AT(1)R protein expression and AT(1)R-mediated increase in intracellular calcium concentration...
February 2014: Hypertension
https://www.readbyqxmd.com/read/24148810/selective-regulation-of-recombinantly-expressed-mglu7-metabotropic-glutamate-receptors-by-g-protein-coupled-receptor-kinases-and-arrestins
#19
L Iacovelli, M Felicioni, R Nisticò, F Nicoletti, A De Blasi
mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway...
February 2014: Neuropharmacology
https://www.readbyqxmd.com/read/23745705/functions-of-third-extracellular-loop-and-helix-8-of-family-b-gpcrs-complexed-with-ramps-and-characteristics-of-their-receptor-trafficking
#20
REVIEW
Kenji Kuwasako, Debbie L Hay, Sayaka Nagata, Manabu Murakami, Kazuo Kitamura, Johji Kato
At least one of three receptor activity-modifying proteins (RAMP1, RAMP2 and RAMP3) can interact with 10 G protein-coupled receptors (GPCRs; nine Family B GPCRs and a Family C GPCR). All three RAMPs interact with the calcitonin (CT) receptor (CTR), the CTR-like receptor (CLR), the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) 1 (VPAC1) and the VPAC2 receptor, which are all Family B GPCRs. Three RAMPs enable CTR to function as three heterodimeric receptors for amylin, which is a feeding suppression peptide...
August 2013: Current Protein & Peptide Science
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