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Protein kinase G

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https://www.readbyqxmd.com/read/29353267/bioactive-pyrrole-alkaloids-isolated-from-the-red-sea-marine-sponge-stylissa-carteri
#1
Ashraf N E Hamed, Roland Schmitz, Anja Bergermann, Frank Totzke, Michael Kubbutat, Werner E G Müller, Diaa T A Youssef, Mokhtar M Bishr, Mohamed S Kamel, RuAngelie Edrada-Ebel, Wim Wätjen, Peter Proksch
Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (±) ageliferin and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-) clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z-spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4-bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated derivatives viz...
January 20, 2018: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/29349619/1h-15n-and-13c-chemical-shift-assignments-of-the-micelle-immersed-fat-c-terminal-fatc-domains-of-the-human-protein-kinases-ataxia-telangiectasia-mutated-atm-and-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs-fused-to-the-b1-domain-of-streptococcal
#2
Munirah S Abd Rahim, Lisa A M Sommer, Anja Wacker, Martin Schaad, Sonja A Dames
FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent NMR- and CD-monitored interaction studies indicated that the FATC domains of all PIKKs can interact with membrane mimetics albeit with different preferences for membrane properties such as surface charge and curvature. Thus they may generally act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical shift assignments of the DPC micelle immersed FATC domains of the human PIKKs ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue long B1 domain of Streptococcal protein G (GB1)...
January 18, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29348847/distinct-roles-of-traf6-and-tak1-in-the-regulation-of-adipocyte-survival-thermogenesis-program-and-high-fat-diet-induced-obesity
#3
Yann S Gallot, Joseph D McMillan, Guangyan Xiong, Kyle R Bohnert, Alex R Straughn, Bradford G Hill, Ashok Kumar
Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#4
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348267/toll-like-receptor-9-dependent-ampk%C3%AE-activation-occurs-via-tak1-and-contributes-to-rhoa-rock-signaling-and-actin-polymerization-in-vascular-smooth-muscle-cells
#5
Cameron G McCarthy, Camilla Ferreira Wenceslau, Safia Ogbi, Theodora Szasz, R Clinton Webb
Traditionally, Toll-like receptor (TLR)9 signals through a MyD88-dependent cascade that results in pro-inflammatory gene transcription. Recently it was reported that TLR9 also participates in a stress tolerance signaling cascade in non-immune cells. In this non-canonical pathway, TLR9 binds to and inhibits sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating intracellular calcium handling, and subsequently resulting in the activation of 5'-AMP-activated protein kinase (AMPK)α. We have previously reported TLR9 causes increased contraction in isolated arteries; however, the mechanisms underlying this vascular dysfunction need to be further clarified...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29348172/-the-a-arrestin-arrdc3-suppresses-breast-carcinoma-invasion-by-regulating-g-protein-coupled-receptor-lysosomal-sorting-and-signaling
#6
Aleena K S Arakaki, Wen-An Pan, Huilan Lin, JoAnn Trejo
Aberrant G protein-coupled receptor (GPCR) expression and activation has been linked to tumor initiation, progression, invasion and metastasis. However, compared with other cancer drivers, the exploitation of GPCRs as potential therapeutic targets has been largely ignored, despite the fact that GPCRs are highly druggable. Therefore, to advance the potential status of GPCRs as therapeutic targets, it is important to understand how GPCRs function together with other cancer drivers during tumor progression. We now report that the alpha-arrestin domain-containing protein-3 (ARRDC3) acts as a tumor suppressor in part by controlling signaling and trafficking of the GPCR, protease-activated receptor-1 (PAR1)...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29344218/atra-increases-iodine-uptake-and-inhibits-the-proliferation-and-invasiveness-of-human-anaplastic-thyroid-carcinoma-sw1736-cells-involvement-of-%C3%AE-catenin-phosphorylation-inhibition
#7
Ling Lan, Spyros Basourakos, Dai Cui, Xuemei Zuo, Wei Deng, Lili Huo, Hailing Chen, Guoying Zhang, Lili Deng, Bingyin Shi, Yong Luo
All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid tumors, but the mechanisms remain poorly understood. The aim of the present study was to investigate the effects of ATRA on isotope susceptibility, proliferation and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms. SW1736 cells were treated with 1 µmol/l ATRA or 1% ethanol for 5 days. A cell line stably expressing β-catenin-shRNA was established. An iodine uptake assay was performed using 125I. Proliferation and invasiveness were tested using MTT and Transwell assays, respectively...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344147/systematic-analysis-of-the-molecular-mechanism-of-microrna-124-in-hepatoblastoma-cells
#8
Guiming Wang, Hong Liu, Zhigang Wei, Hongyan Jia, Yu Liu, Jiansheng Liu
The present study aimed to identify the molecular mechanisms of microRNA-124 (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained from the Gene Expression Omnibus database, included samples extracted from HepG2 cells transfected with miR-124 duplex (the experimental group) or negative control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection. Differentially expressed genes (DEGs) were screened between the two groups. miR-124 activity was inferred based on the expression of its target genes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344142/isolation-and-identification-of-tumor-initiating-cell-properties-in-human-gallbladder-cancer-cell-lines-using-the-marker-cluster-of-differentiation-133
#9
Jiwei Yu, Zhaohui Tang, Wei Gong, Mingdi Zhang, Zhiwei Quan
The present study aimed to isolate and identify the properties of the cluster of differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic separation, and the biological features of the two subpopulations were analyzed in vitro and in vivo. In particular, the present study aimed to determine whether the two subpopulations were resistant to anti-tumor reagents and to identify the underlying molecular mechanisms involved...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343805/biallelic-variants-in-kif14-cause-intellectual-disability-with-microcephaly
#10
Periklis Makrythanasis, Reza Maroofian, Asbjørg Stray-Pedersen, Damir Musaev, Maha S Zaki, Iman G Mahmoud, Laila Selim, Amera Elbadawy, Shalini N Jhangiani, Zeynep H Coban Akdemir, Tomasz Gambin, Hanne S Sorte, Arvid Heiberg, Jennifer McEvoy-Venneri, Kiely N James, Valentina Stanley, Denice Belandres, Michel Guipponi, Federico A Santoni, Najmeh Ahangari, Fatemeh Tara, Mohammad Doosti, Justyna Iwaszkiewicz, Vincent Zoete, Paul Hoff Backe, Hanan Hamamy, Joseph G Gleeson, James R Lupski, Ehsan Ghayoor Karimiani, Stylianos E Antonarakis
Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p...
January 17, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29343782/protein-phosphatase-5-regulates-titin-phosphorylation-and-function-at-a-sarcomere-associated-mechanosensor-complex-in-cardiomyocytes
#11
Judith Krysiak, Andreas Unger, Lisa Beckendorf, Nazha Hamdani, Marion von Frieling-Salewsky, Margaret M Redfield, Cris G Dos Remedios, Farah Sheikh, Ulrich Gergs, Peter Boknik, Wolfgang A Linke
Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343719/the-significant-role-of-c-abl-kinase-in-barrier-altering-agonists-mediated-cytoskeletal-biomechanics
#12
X Wang, L Wang, J G N Garcia, S M Dudek, G S Shekhawat, V P Dravid
Exploration of human pulmonary artery endothelial cell (EC) as a prototypical biomechanical system has important pathophysiologic relevance because this cell type plays a key role in the development of a wide variety of clinical conditions. The complex hierarchical organization ranging from the molecular scale up to the cellular level has an intimate and intricate relationship to the barrier function between lung tissue and blood. To understand the innate molecule-cell-tissue relationship across varied length-scales, the functional role of c-Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier-altering agonists was investigated using atomic force microscopy...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29340786/in-silico-identification-and-experimental-validation-of-amino-acid-motifs-required-for-the-rho-of-plants-gtpase-mediated-activation-of-receptor-like-cytoplasmic-kinases
#13
Dézi Bianka Lajkó, Ildikó Valkai, Mónika Domoki, Dalma Ménesi, Györgyi Ferenc, Ferhan Ayaydin, Attila Fehér
Several amino acid motifs required for Rop-dependent activity were found to form a common surface on RLCKVI_A kinases. This indicates a unique mechanism for Rho-type GTPase-mediated kinase activation in plants. Rho-of-plants (Rop) G-proteins are implicated in the regulation of various cellular processes, including cell growth, cell polarity, hormonal and pathogen responses. Our knowledge about the signalling pathways downstream of Rops is continuously increasing. However, there are still substantial gaps in this knowledge...
January 16, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29340527/cardiac-protein-expression-patterns-are-associated-with-distinct-inborn-exercise-capacity-in-non-selectively-bred-rats
#14
L P Ribeiro, L C Freitas-Lima, G B Naumann, S S Meyrelles, W Lunz, S F Pires, H M Andrade, J B T Carnielli, S G Figueiredo
In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV) tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP) and high running performance (HRP) rats were categorized by a treadmill exercise test, according to distance run to exhaustion...
January 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#15
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339457/curcumin-acts-as-a-positive-allosteric-modulator-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-reverses-nociception-in-mouse-models-of-inflammatory-pain
#16
Eslam Gaber El Nebrisi, Deniz Bagdas, Wisam Toma, Halima Al Samri, Anna Brodzik, Yasmin Alkhlaif, Keun-Hang Susan Yang, Frank C Howarth, Imad M Damaj, Murat Oz
Effects of curcumin, a major ingredient of turmeric, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of ACh (100 μM)-induced currents with an EC50 value of 0.2 µM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca2+-dependent Cl- channels expressed endogenously in oocytes...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29339045/deficiency-of-dietary-pyridoxine-disturbed-the-intestinal-physical-barrier-function-of-young-grass-carp-ctenopharyngodon-idella
#17
Pei Wu, Xin Zheng, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Yong-An Zhang, Lin Feng
The aim of this study was to assess the effects of dietary pyridoxine (PN) deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular tight junction in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (231.85 ± 0.63 g) were fed six diets containing graded levels of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed that compared with the optimal PN level, PN deficiency (1) increased the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), decreased the activities and mRNA levels of antioxidant enzymes such as copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) (P < ...
January 12, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29337365/loss-of-sti1-mediated-neuronal-survival-and-differentiation-in-disease-associated-mutations-of-prion-protein
#18
M C Landemberger, G P Oliveira, C F Machado, K J Gollob, V R Martins
Cellular prion protein (PrPC ) is widely expressed and displays a variety of well-described functions in the central nervous system (CNS). Mutations of the PRNP gene are known to promote genetic human spongiform encephalopathies, but the components of gain- or loss-of-function mutations to PrPC remain a matter for debate. Among the proteins described to interact with PrPC is stress inducible protein 1 (STI1), a co-chaperonin that is secreted from astrocytes and triggers neuroprotection and neuritogenesis through its interaction with PrPC ...
January 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29337352/genetic-removal-of-eif2%C3%AE-kinase-perk-in-mice-enables-hippocampal-l-ltp-independent-of-mtorc1-activity
#19
Helena R Zimmermann, Wenzhong Yang, Brenna C Beckelman, Nicole P Kasica, Xueyan Zhou, Lucas Galli, Alexey G Ryazanov, Tao Ma
Characterization of the molecular signaling pathways underlying protein synthesis-dependent forms of synaptic plasticity, such as late long-term potentiation (L-LTP), can provide insights not only into memory expression/maintenance under physiological conditions but also potential mechanisms associated with the pathogenesis of memory disorders. Here, we report in mice that L-LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2α (eIF2α)...
January 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29337245/hepatic-alcohol-dehydrogenase-deficiency-induces-pancreatic-injury-in-chronic-ethanol-feeding-model-of-deer-mice
#20
Samir M Amer, Kamlesh K Bhopale, Ramu D Kakumanu, Vsevolod L Popov, Bill A Rampy, Inas H El-Mehallawi, Magdy M Ashmawy, G A Shakeel Ansari, Bhupendra S Kaphalia
The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH- deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP)...
January 11, 2018: Experimental and Molecular Pathology
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