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Protein kinase G

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https://www.readbyqxmd.com/read/28526706/cardiac-hyporesponsiveness-in-severe-sepsis-is-associated-with-nitric-oxide-dependent-activation-of-g-protein-receptor-kinase
#1
Daniela Dal-Secco, Silvia DalBó, Natalia E S Lautherbach, Fábio N Gava, Mara Rubia Nunes Celes, Patricia Oliveira Benedet, Adriana H Souza, Juliana Akinaga, Vanessa Lima, Katiussia P Silva, Luiz Ricardo A Kiguti, Marcos A Rossi, Isis do Carmo Kettelhut, André Sampaio Pupo, Fernando Queiroz Cunha, Jamil Assreuy
G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS-2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP)...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28526450/the-association-of-single-nucleotide-polymorphisms-in-the-oxytocin-receptor-and-g-protein-coupled-receptor-kinase-6-grk6-genes-with-oxytocin-dosing-requirements-and-labor-outcomes
#2
Chad A Grotegut, Emily Ngan, Melanie E Garrett, Marie Lynn Miranda, Allison E Ashley-Koch, Geeta K Swamy
BACKGROUND: Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. OBJECTIVE: The objective of this study was to determine if genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the OXTR, could explain variation in oxytocin dosing and labor outcomes among women being induced near term...
May 16, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#3
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28524165/molecular-assembly-of-rhodopsin-with-g-protein-coupled-receptor-kinases
#4
Yuanzheng He, Xiang Gao, Devrishi Goswami, Li Hou, Kuntal Pal, Yanting Yin, Gongpu Zhao, Oliver P Ernst, Patrick Griffin, Karsten Melcher, H Eric Xu
G protein-coupled receptor kinases (GRKs) play pivotal roles in desensitizing GPCR signaling but little is known about how GRKs recognize and phosphorylate GPCRs due to the technical difficulties in detecting the highly dynamic GPCR/GRK interaction. By combining a genetic approach with multiple biochemical assays, we identified the key determinants for the assembly of the prototypical GPCR rhodopsin with its kinase GRK1. Our work reveals that the regulatory G-protein signaling homology (RH) domain of GRKs is the primary binding site to GPCRs and an active conformation of the GRK1 kinase domain is required for efficient interaction with rhodopsin...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28522753/cyclin-d1-restrains-oncogene-induced-autophagy-by-regulating-the-ampk-lkb1-signaling-axis
#5
Mathew C Casimiro, Gabriele Di Sante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Tim Pestell, Sara Bisetto, Marco A Velasco-Velàzquez, Xuanmao Jiao, Zhiping Li, Christine M Kusminski, Erin L Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E Scherer, Richard G Pestell
Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclinD1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that Cyclin D1 inhibited mitochondrial function, promoted glycolysis and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#6
Wei-Chun J Hsu, Norelle Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jai Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
May 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28521058/enhanced-expression-of-proteins-involved-in-energy-production-and-transfer-in-breast-muscle-of-pedigree-male-broilers-exhibiting-high-feed-efficiency
#7
W G Bottje, K Lassiter, S Dridi, N Hudson, B-W Kong
In cells with fluctuating energy demand (e.g., skeletal muscle), a transfer system of proteins across the inner and outer mitochondrial membranes links mitochondrial oxidative phosphorylation to cytosolic phosphorylated creatine (PCr) that serves as a phosphate reservoir for rapid repletion of cytosolic adenosine triphosphate (ATP). Crucial proteins of this energy transfer system include several creatine kinase (CK) isoforms found in the cytosol and mitochondria. In a recent proteomic study (Kong et al., 2016), several components of this system were up-regulated in high feed efficiency (FE) compared to low FE breast muscle; notably adenine nucleotide translocase (ANT), voltage dependent activated channel (VDAC), the brain isoform of creatine kinase (CK-B), and several proteins of the electron transport chain...
May 17, 2017: Poultry Science
https://www.readbyqxmd.com/read/28516374/role-of-lps-elicited-signaling-in-triggering-gastric-mucosal-inflammatory-responses-to-h-pylori-modulatory-effect-of-ghrelin
#8
REVIEW
B L Slomiany, A Slomiany
Infection with Helicobacter pylori is a primary culprit in the etiology of gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a potent endotoxin responsible for triggering a pattern of the mucosal inflammatory responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4 (TLR4) leads to initiation of signal transduction events characterized by the activation of mitogen-activated protein kinase (MAPK) cascade, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt...
May 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28516266/constitutive-calcium-entry-and-cancer-updated-views-and-insights
#9
REVIEW
Olivier Mignen, Bruno Constantin, Marie Potier-Cartereau, Aubin Penna, Mathieu Gautier, Maxime Guéguinou, Yves Renaudineau, Kenji F Shoji, Romain Félix, Elsa Bayet, Paul Buscaglia, Marjolaine Debant, Aurélie Chantôme, Christophe Vandier
Tight control of basal cytosolic Ca(2+) concentration is essential for cell survival and to fine-tune Ca(2+)-dependent cell functions. A way to control this basal cytosolic Ca(2+) concentration is to regulate membrane Ca(2+) channels including store-operated Ca(2+) channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca(2+) channels involved...
May 17, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28515323/%C3%AE-adrenergic-induction-of-lipolysis-in-hepatocytes-is-inhibited-by-ethanol-exposure
#10
Micah B Schott, Karuna Rasineni, Shaun G Weller, Ryan J Schulze, Arthur C Sletten, Carol A Casey, Mark A McNiven
In liver steatosis i.e., fatty liver), hepatocytes accumulate many large neutral lipid-storage organelles known as lipid droplets (LDs). LDs are important in the maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines target the β-adrenergic (β-AR)/cAMP pathway to activate cytosolic lipases and induce their recruitment to the LD surface. Therefore, the goal of this study was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated lipolysis in response to β-AR stimulation...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515165/zinc-supplementation-via-gpr39-upregulates-pkc%C3%AE-to-protect-intestinal-barrier-integrity-in-caco-2-cells-challenged-by-salmonella-enterica-serovar-typhimurium
#11
Yu-Xin Shao, Zhao Lei, Patricia G Wolf, Yan Gao, Yu-Ming Guo, Bing-Kun Zhang
Background: Zinc has been shown to improve intestinal barrier function against Salmonella enterica serovar Typhimurium (S. typhimurium) infection, but the mechanisms involved in this process remain undefined.Objective: We aimed to explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Cζ (PKCζ) in the regulation by zinc of intestinal barrier function.Methods: A Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 μM Zn and then incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small interfering RNA for GPR39 or PKCζ were pretreated with 100 μM Zn and incubated with S...
May 17, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28513979/identification-of-a-de-novo-variant-in-chuk-in-a-patient-with-an-eec-aec-syndrome-like-phenotype-and-hypogammaglobulinemia
#12
Kriti D Khandelwal, Charlotte W Ockeloen, Hanka Venselaar, Cécile Boulanger, Bénédicte Brichard, Etienne Sokal, Rolph Pfundt, Tuula Rinne, Ellen van Beusekom, Marjon Bloemen, Gerrit Vriend, Nicole Revencu, Carine E L Carels, Hans van Bokhoven, Huiqing Zhou
The cardinal features of Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate (EEC), and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndromes are ectodermal dysplasia (ED), orofacial clefting, and limb anomalies. EEC and AEC are caused by heterozygous mutations in the transcription factor p63 encoded by TP63. Here, we report a patient with an EEC/AEC syndrome-like phenotype, including ankyloblepharon, ED, cleft palate, ectrodactyly, syndactyly, additional hypogammaglobulinemia, and growth delay...
May 17, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28513773/attenuation-of-renal-ischemic-reperfusion-injury-by-salvianolic-acid-b-via-suppressing-oxidative-stress-and-inflammation-through-pi3k-akt-signaling-pathway
#13
Z G Ma, H Q Xia, S L Cui, J Yu
Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28512645/regulation-of-discrete-functional-responses-by-syk-and-src-family-tyrosine-kinases-in-human-neutrophils
#14
Thornin Ear, Olga Tatsiy, Frédérick L Allard, Patrick P McDonald
Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28512244/engineering-and-functional-characterization-of-fusion-genes-identifies-novel-oncogenic-drivers-of-cancer
#15
Hengyu Lu, Nicole Villafane, Turgut Dogruluk, Caitlin L Grzeskowiak, Kathleen Kong, Yiu Huen Tsang, Oksana Zagorodna, Angeliki Pantazi, Lixing Yang, Nicholas J Neill, Young Won Kim, Chad J Creighton, Roel G Verhaak, Gordon B Mills, Peter Park, Raju S Kucherlapati, Kenneth L Scott
Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28512242/a-systematic-analysis-of-oncogenic-gene-fusions-in-primary-colon-cancer
#16
Wigard P Kloosterman, Robert R J Coebergh van den Braak, Mark Pieterse, Markus J van Roosmalen, Anieta M Sieuwerts, Christina Stangl, Ronne Brunekreef, Zarina S Lalmahomed, Salo Ooft, Anne van Galen, Marcel Smid, Armel Lefebvre, Fried Zwartkruis, John W M Martens, John A Foekens, Katharina Biermann, Marco J Koudijs, Jan N M IJzermans, Emile E Voest
Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511982/characteristic-and-intermingled-neocortical-circuits-encode-different-visual-object-discriminations
#17
Guo-Rong Zhang, Hua Zhao, Nathan Cook, Michael Svestka, Eui M Choi, Mary Jan, Robert G Cook, Alfred I Geller
Synaptic plasticity and neural network theories hypothesize that the essential information for advanced cognitive tasks is encoded in specific circuits and neurons within distributed neocortical networks. However, these circuits are incompletely characterized, and we do not know if a specific discrimination is encoded in characteristic circuits among multiple animals. Here, we determined the spatial distribution of active neurons for a circuit that encodes some of the essential information for a cognitive task...
May 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#18
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28509555/differential-phosphoproteomic-analysis-of-recombinant-chinese-hamster-ovary-cells-following-temperature-shift
#19
Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis and signal transduction. However, to date little work has been carried out on the phosphoproteome in CHO cells. In this study we have carried out a large scale differential phosphoproteomic analysis of recombinant CHO cells following a reduction of culture temperature (temperature shift)...
May 16, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#20
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
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