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Protein kinase G

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https://www.readbyqxmd.com/read/28820778/src-kinase-inhibition-attenuates-morphine-tolerance-without-affecting-reinforcement-or-psychomotor-stimulation
#1
Fiona A Bull, Daniel T Baptista-Hon, Claire Sneddon, Lisa Wright, Wendy Walwyn, Tim G Hales
BACKGROUND: Prolonged opioid administration leads to tolerance characterized by reduced analgesic potency. Pain management is additionally compromised by the hedonic effects of opioids, the cause of their misuse. The multifunctional protein β-arrestin2 regulates the hedonic effects of morphine and participates in tolerance. These actions might reflect µ opioid receptor up-regulation through reduced endocytosis. β-Arrestin2 also recruits kinases to µ receptors. We explored the role of Src kinase in morphine analgesic tolerance, locomotor stimulation, and reinforcement in C57BL/6 mice...
August 18, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28820400/alteration-in-expressions-of-rhoa-and-rho-kinases-during-pregnancy-in-rats-their-roles-in-uterine-contractions-and-onset-of-labour
#2
D Domokos, E Ducza, G Falkay, R Gaspar
Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis. The other purpose was to evaluate the effects of the ROCK (Y-27632, fasudil and RKI 1441) and RhoA inhibitors (simvastatin) on uterine contractility in isolated organ bath experiments...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819396/expression-and-significances-of-g-protein-coupled-receptor-kinase-3-in-hepatocellular-carcinoma
#3
Ye Jin, Zhi-Yong Liang, Wei-Xun Zhou, Li Zhou
Objective: To investigate expression, clinical, pathologic and prognostic significances of G-protein-coupled receptor kinase 3 (GRK3) in hepatocellular carcinoma (HCC). Materials and Methods: Expression of GRK3 was detected using Western blotting and tissue microarray-based immunohistochemical staining in 8 and 395 patients (training set: n=164; validation set: n=231) with HCC underwent hepatectomy, respectively. GRK3 expression and its associations with cliniopathologic variables and tumor-specific survival were evaluated...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818508/the-role-of-the-il-8-signaling-pathway-in-the-infiltration-of-granulocytes-into-the-livers-of-patients-with-alcoholic-hepatitis
#4
S W French, A S Mendoza, N Afifiyan, B Tillman, E Vitocruz, B A French
BACKGROUND AND AIM: IL-8 (C-X-L motif chemokine ligase 8) and CXCR2 (C-X-C-motif chemokine receptor 2) are up regulated in alcoholic hepatitis (AH) liver biopsies. One of the consequences is the attraction and chemotactic neutrophilic infiltrate seen at the AH stage of alcoholic liver disease. MATERIALS AND METHODS: Human formalin-fixed, paraffin-embedded (FFPE) liver biopsies from patients who have AH were studied by (2.1) RNA sequencing, (2.2) PCR and (2.3) semi quantitation of specific proteins in biopsy sections using immunohistochemical measurements of antibody fluorescent intensity with morphometric technology...
August 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28818206/pharmacological-and-activated-fibroblast%C3%A2-targeting-of-g%C3%AE-%C3%AE-grk2-after%C3%A2-myocardial-ischemia-attenuates-heart-failure-progression
#5
Joshua G Travers, Fadia A Kamal, Iñigo Valiente-Alandi, Michelle L Nieman, Michelle A Sargent, John N Lorenz, Jeffery D Molkentin, Burns C Blaxall
BACKGROUND: Cardiac fibroblasts are a critical cell population responsible for myocardial extracellular matrix homeostasis. Upon injury or pathological stimulation, these cells transform to an activated myofibroblast state and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation, a hallmark of heart failure (HF), induces pathological signaling through G protein βγ (Gβγ) subunits and their interaction with G protein-coupled receptor kinase 2 (GRK2)...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28816422/dolichol-kinase-deficiency-dolk-cdg-two-new-cases-and-expansion-of-phenotype
#6
Eric T Rush, Craig V Baker, William B Rizzo
Congenital disorders of glycosylation (CDGs) are a group of genetic diseases caused by mutations in genes that are necessary for the addition of oligosaccharides to acceptor proteins or lipids. An early step in this process requires dolichol kinase (DK) to catalyze the formation of dolichyl phosphate, which acts as a membrane anchor for initial attachment of sugar residues that are subsequently built up to oligosaccharides and transferred to acceptor proteins and lipids for further processing. Biallelic mutations in DOLK, the gene for DK, result in human in a CDG with variable symptoms, ranging from nonsyndromic dilated cardiomypopathy to severe multiorgan involvement...
September 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#7
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28815513/an-update-on-p2y13-receptor-signalling-and-function
#8
Raquel Pérez-Sen, Rosa Gómez-Villafuertes, Felipe Ortega, Javier Gualix, Esmerilda G Delicado, María Teresa Miras-Portugal
The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y13 is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y12 and P2Y14. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y12 receptors but with unique features and roles. The P2RY12-14 genes all reside on human chromosome 3 at 3q25...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814763/spatial-genomic-heterogeneity-in-multiple-myeloma-revealed-by-multi-region-sequencing
#9
L Rasche, S S Chavan, O W Stephens, P H Patel, R Tytarenko, C Ashby, M Bauer, C Stein, S Deshpande, C Wardell, T Buzder, G Molnar, M Zangari, F van Rhee, S Thanendrarajan, C Schinke, J Epstein, F E Davies, B A Walker, T Meissner, B Barlogie, G J Morgan, N Weinhold
In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes...
August 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28814745/suppression-of-grk2-expression-reduces-endothelial-dysfunction-by-restoring-glucose-homeostasis
#10
Kumiko Taguchi, Mari Hida, Mami Hasegawa, Haruka Narimatsu, Takayuki Matsumoto, Tsuneo Kobayashi
Despite the associations between diabetic complications and vascular endothelial dysfunction, a direct therapeutic method targeting endothelial dysfunction remains poorly characterized. We have previously shown that chemical inhibition of G-protein-coupled receptor kinase 2 (GRK2) slightly enhances insulin sensitivity and reduces endothelial dysfunction in type 2 diabetic mice. In this study, we identified GRK2 as a novel therapeutic target of diabetic endothelial dysfunction and investigated the effect on diabetic endothelial dysfunction through the systemic administration of GRK2 siRNA using a hydrodynamic-based procedure, resulting in suppression of increased GRK2 protein levels in the liver...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814525/structure-guided-functional-annotation-of-the-influenza-a-virus-ns1-protein-reveals-dynamic-evolution-of-the-p85%C3%AE-binding-site-during-circulation-in-humans
#11
Antonio M Lopes, Patricia Domingues, Roland Zell, Benjamin G Hale
Rational characterization of virulence and host-adaptive markers in the multifunctional influenza A virus NS1 protein is hindered by a lack of comprehensive knowledge about NS1-host protein-protein interfaces. Here, we surveyed the impact of amino-acid variation in NS1 at its structurally-defined binding site for host p85β, a regulator of phosphoinositide-3 kinase (PI3K) signaling. Structure-guided alanine-scanning of all viral residues at this interface defined 10 positions contributing to the interaction, with residues 89, 95, 98, 133, 145 and 162 being most important...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813514/the-helicobacter-pylori-type-iv-secretion-system-promotes-il-8-synthesis-in-a-model-of-pediatric-airway-epithelium-via-p38-map-kinase
#12
Myra G Dela Pena-Ponce, Monica T Jimenez, Lori M Hansen, Jay V Solnick, Lisa A Miller
Epidemiologic studies have reported an inverse relationship between childhood Helicobacter pylori infection and development of allergic asthma. Because lung epithelium plays an important role in allergic asthma pathogenesis, we hypothesized that H. pylori may directly influence airway epithelial cell innate immune function, particularly in early childhood. To test our hypothesis, we established an in vitro H. pylori infection model using primary tracheobronchial epithelial cell cultures derived from infant, juvenile and adult rhesus monkeys...
2017: PloS One
https://www.readbyqxmd.com/read/28810562/anti-depressant-like-effects-of-jieyu-chufan-capsules-in-a-mouse-model-of-unpredictable-chronic-mild-stress
#13
Hui Zhao, Bingyu Liang, Linjie Yu, Yun Xu
Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810331/-effect-of-tsc2-gene-expression-downregulation-by-lentivirus-induced-rna-interference-on-u937-cell-line-and-its-mechanism
#14
Z F Xu, H X Liu, Y H Tan, X H Chen, F G Ren, Y F Zhang, J M Chang, N Zhang, J J Hu, H W Wang
Objective: To investigate the effect of biology and mTOR pathway activity of down-regulated TSC2 gene expression on U937 leukemia cells. Methods: Gene expression was down-regulated by lentivirus induced RNA interference on TSC2 high expressed U937 cell line; the proliferation, apoptosis and differentiation were detected by CCK-8 assay, colony formation assay and flow cytometry; the gene expression level and protein kinase activity were detected by qRT-PCR and Western blot. Results: Down-regulated expression of TSC2 gene promoted U937 cell proliferation and colony formation ability (P<0...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808993/multiplexed-liquid-chromatography-multiple-reaction-monitoring-mass-spectrometry-quantification-of-cancer-signaling-proteins
#15
Yi Chen, Kate J Fisher, Mark Lloyd, Elizabeth R Wood, Domenico Coppola, Erin Siegel, David Shibata, Yian A Chen, John M Koomen
Quantitative evaluation of protein expression across multiple cancer-related signaling pathways (e.g., Wnt/β-catenin, TGF-β, receptor tyrosine kinases (RTK), MAP kinases, NF-κB, and apoptosis) in tumor tissues may enable the development of a molecular profile for each individual tumor that can aid in the selection of appropriate targeted cancer therapies. Here, we describe the development of a broadly applicable protocol to develop and implement quantitative mass spectrometry assays using cell line models and frozen tissue specimens from colon cancer patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808226/atr-inhibition-facilitates-targeting-of-leukemia-dependence-on-convergent-nucleotide-biosynthetic-pathways
#16
Thuc M Le, Soumya Poddar, Joseph R Capri, Evan R Abt, Woosuk Kim, Liu Wei, Nhu T Uong, Chloe M Cheng, Daniel Braas, Mina Nikanjam, Peter Rix, Daria Merkurjev, Jesse Zaretsky, Harley I Kornblum, Antoni Ribas, Harvey R Herschman, Julian Whitelegge, Kym F Faull, Timothy R Donahue, Johannes Czernin, Caius G Radu
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#17
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808155/roca-is-an-accessory-protein-to-the-virulence-regulating-covr-s-two-component-system-in-the-group-a-streptococcus
#18
Ira Jain, Eric W Miller, Jessica L Danger, Kathryn J Pflughoeft, Paul Sumby
Regulating gene expression during infection is critical to the ability of pathogens to circumvent the immune response and cause disease. This is true for the group A Streptococcus (GAS), a pathogen that causes both invasive (e.g. necrotizing fasciitis) and non-invasive (e.g. pharyngitis) diseases. The control of virulence (CovR/S) two-component system has a major role in regulating GAS virulence factor expression. The regulator of cov (RocA) protein, which is a predicted kinase, functions in an undetermined manner through CovR/S to alter gene expression and reduce invasive disease virulence...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28808138/an-ampk-dependent-regulatory-pathway-in-tau-mediated-toxicity
#19
Alessia Galasso, Charles S Cameron, Bruno G Frenguelli, Kevin G Moffat
Neurodegenerative tauopathies are characterized by accumulation of hyperphosphorylated tau aggregates primarily degraded by autophagy.The 5'AMP-activated protein kinase (AMPK) is expressed in most cells, including neurons. Alongside its metabolic functions, it is also known to be activated in Alzheimer's brains, phosphorylate tau and be a critical autophagy activator. Whether it plays a neurotoxic or neuroprotective role remains unclear. Complexly in tauopathies, while stress conditions can result in AMPK activation enhancing tau-mediated toxicity, AMPK activation is not always concomitant with autophagic induction...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28808053/navigating-the-conformational-landscape-of-g-protein-coupled-receptor-kinases-during-allosteric-activation
#20
Xin-Qiu Yao, M Claire Cato, Emily Labudde, Tyler S Beyett, John J G Tesmer, Barry J Grant
G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family...
August 14, 2017: Journal of Biological Chemistry
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