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Protein Kinase

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https://www.readbyqxmd.com/read/28735419/modulation-of-human-kv4-3-kchip2-channel-inactivation-kinetics-by-cytoplasmic-ca-2
#1
Christiane Groen, Robert Bähring
The transient outward current (I to) in the human heart is mediated by Kv4.3 channels complexed with Kv channel interacting protein (KChIP) 2, a cytoplasmic Ca(2+)-binding EF-hand protein known to modulate Kv4.3 inactivation gating upon heterologous co-expression. We studied Kv4.3 channels co-expressed with wild-type (wt) or EF-hand-mutated (ΔEF) KChIP2 in human embryonic kidney (HEK) 293 cells. Co-expression took place in the absence or presence of BAPTA-AM, and macroscopic currents were recorded in the whole-cell patch-clamp configuration with different free Ca(2+) concentrations in the patch-pipette...
July 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28735398/phosphoproteomics-analysis-for-probing-plant-stress-tolerance
#2
Christof Rampitsch
Protein phosphorylation is a key signaling mechanism during the plant biotic and abiotic stress response. Signaling cascades communicate between the cell surface, where the stress is perceived, and the nucleus, where a response can be enacted. Many of these signals involve the specific, transient phosphorylation of proteins by kinases, a signal which is usually amplified through cascades. The advent of high-throughput phosphoproteomics, pioneered mainly in yeast and mammalian cells, has made it possible to discover novel phosphorylation events rapidly and efficiently in a data-dependent manner and this has greatly enlarged our understanding of the plant's response to stress...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735374/changes-in-global-transcriptional-profiling-of-women-following-obesity-surgery-bypass
#3
Marcela Augusta de Souza Pinhel, Natalia Yumi Noronha, Carolina Ferreira Nicoletti, Bruno Affonso Parente de Oliveira, Cristiana Cortes-Oliveira, Vitor Caressato Pinhanelli, Wilson Salgado Junior, Ana Julia Machry, Wilson Araújo da Silva Junior, Dorotéia Rossi Silva Souza, Júlio Sérgio Marchini, Carla Barbosa Nonino
BACKGROUND: Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss. METHODS: The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control...
July 22, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28734998/oxidative-stress-with-tau-hyperphosphorylation-in-memory-impaired-1-2-diacetylbenzene-treated-mice
#4
Sin-Woo Kang, Sung Jin Kim, Min-Sun Kim
Long-term exposure to organic solvent may be related to the incidence of neuronal diseases, such as, Alzheimer's disease, depression, multiple sclerosis, dementia, Parkinson's disease. Previously, the authors reported 1,2-diacetylbenzene (DAB; a neurotoxic metabolite of 1,2-diethylbenzene) causes central and peripheral neuropathies that lead to motor neuronal deficits. Furthermore, it is known DAB increases oxidative stress and protein adduct levels and impairs hippocampal neurogenesis in mice. The authors examined the relevance of oxidative stress and tau hyperphosphorylation in the hippocampus...
July 19, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28734942/calcium-calmodulin-dependent-protein-kinase-iv-gene-polymorphisms-in-korean-alcohol-dependent-patients
#5
Jung Woo-Young, Kim Sung-Gon, Kim Ji-Hoon, Lee Jin-Seong
INTRODUCTION: A relationship between alcohol dependence (AD) and calcium/calmodulin-dependent protein kinase IV (CAMKIV) has been reported in a whole genome study of Korean AD patients. The purpose of the present study is to compare the frequency of CAMKIV genotypes and alleles between AD and control subjects in Korea. METHODS: The present study includes 281 AD patients and 139 control subjects. Seven single nucleotide polymorphism of CAMKIV gene known to show significant separation ratio in Asians were searched in SNP database and previous studies related to CAMKIV gene...
July 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28734845/leveraging-siglec-8-endocytic-mechanisms-to-kill-human-eosinophils-and-malignant-mast-cells
#6
Jeremy A O'Sullivan, Daniela J Carroll, Yun Cao, Adriano N Salicru, Bruce S Bochner
BACKGROUND: Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectively on human eosinophils, mast cells, and basophils, making it an ideal target for the treatment of diseases involving these cell types. However, the effective delivery of therapeutic agents to these cells requires an understanding of the dynamics of Siglec-8 surface expression. OBJECTIVE: To determine whether Siglec-8 is endocytosed in human eosinophils and malignant mast cells, identify mechanisms underlying its endocytosis, and demonstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells...
July 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28734766/trpv1-modulates-morphine-induced-conditioned-place-preference-via-p38-mapk-in-the-nucleus-accumbens
#7
Sa-Ik Hong, Thi-Lien Nguyen, Shi-Xun Ma, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Emerging evidence suggests that the transient receptor potential vanilloid type 1 channel (TRPV1) is a novel target for the treatment of drug addiction, such as cocaine and morphine. Previously we reported that TRPV1 inhibition reduced morphine reward in the dorsal striatum (DSt) of mice and morphine self-administration through a decrease in accumbal activity in rats. However, the role of TRPV1 on morphine-conditioned reward in addiction-related brain regions, such as the nucleus accumbens (NAc), has not been previously established...
July 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28734616/do-shoot-the-messenger-pasta-kinases-as-virulence-determinants-and-antibiotic-targets
#8
REVIEW
Daniel A Pensinger, Adam J Schaenzer, John-Demian Sauer
All domains of life utilize protein phosphorylation as a mechanism of signal transduction. In bacteria, protein phosphorylation was classically thought to be mediated exclusively by histidine kinases as part of two-component signaling systems. However, it is now well appreciated that eukaryotic-like serine/threonine kinases (eSTKs) control essential processes in bacteria. A subset of eSTKs are single-pass transmembrane proteins that have extracellular penicillin-binding-protein and serine/threonine kinase-associated (PASTA) domains which bind muropeptides...
July 19, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28734476/quantifying-the-interaction-between-egfr-dimers-and-grb2-in-live-cells
#9
Nuala Del Piccolo, Kalina Hristova
Adaptor proteins are a class of cytoplasmic proteins that bind to phosphorylated residues in receptor tyrosine kinases and trigger signaling cascades that control critically important cellular processes, such as cell survival, growth, differentiation, and motility. Here, we seek to characterize the interaction between epidermal growth factor receptor (EGFR) and the cytoplasmic adaptor protein growth factor receptor-bound protein 2 (Grb2) in a cellular context. To do so, we explore the utility of a highly biologically relevant model system, mammalian cells under reversible osmotic stress, and a recently introduced Förster resonance energy transfer microscopy method, fully quantified spectral imaging...
July 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28734225/adverse-effects-of-methylmercury-mehg-on-life-parameters-antioxidant-systems-and-mapk-signaling-pathways-in-the-rotifer-brachionus-koreanus-and-the-copepod-paracyclopina-nana
#10
Young Hwan Lee, Duck-Hyun Kim, Hye-Min Kang, Minghua Wang, Chang-Bum Jeong, Jae-Seong Lee
To evaluate the adverse effects of MeHg on the rotifer Brachionus koreanus and the copepod Paracyclopina nana, we assessed the effects of MeHg toxicity on life parameters (e.g. growth retardation and fecundity), antioxidant systems, and mitogen-activated protein kinase (MAPK) signaling pathways at various concentrations (1ng/L, 10ng/L, 100ng/L, 500ng/L, and 1000ng/L). MeHg exposure resulted in the growth retardation with the increased ROS levels but decreased glutathione (GSH) levels in a dose-dependent manner in both B...
July 12, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#11
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28733795/early-response-of-c-reactive-protein-as-a-predictor-of-survival-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#12
Yosuke Yasuda, Kazutaka Saito, Takeshi Yuasa, Sho Uehara, Naoko Kawamura, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Shinya Yamamoto, Tetsuo Okuno, Junji Yonese, Kazunori Kihara, Yasuhisa Fujii
BACKGROUND: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. METHODS: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder)...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#13
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28733613/rnai-screening-identifies-trypanosoma-brucei-stress-response-protein-kinases-required-for-survival-in-the-mouse
#14
Fernando Fernandez-Cortes, Tiago D Serafim, Jonathan M Wilkes, Nathaniel G Jones, Ryan Ritchie, Richard McCulloch, Jeremy C Mottram
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733545/a-small-molecule-inhibitor-targeting-the-aurkc-i%C3%AE%C2%BAb%C3%AE-interaction-decreases-transformed-growth-of-mda-mb-231-breast-cancer-cells
#15
Eun Hee Han, Jin-Young Min, Shin-Ae Yoo, Sung-Joon Park, Yun-Jeong Choe, Hee Sub Yun, Zee-Won Lee, Sun Woo Jin, Hyung Gyun Kim, Hye Gwang Jeong, Hyun Kyoung Kim, Nam Doo Kim, Young-Ho Chung
The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733543/the-role-of-adrenomedullin-in-the-pathogenesis-of-gastric-cancer
#16
Fuhao Qiao, Jian Fang, Jinfeng Xu, Wenqiu Zhao, Ying Ni, Bufugdi Andreas Akuo, Wei Zhang, Yun Liu, Fangfang Ding, Guanlin Li, Baoguo Liu, Hua Wang, Shihe Shao
Adrenomedullin has been shown to be overexpressed in many tumors, including gastric cancer tumors; however, its mechanism of action remains unclear. In this study, we examined the role of adrenomedullin in the pathogenesis of gastric cancer. Using clinical specimens and immunohistochemistry, we found that the expression levels of adrenomedullin and its receptors are inordinately elevated as compared to the adjacent non-tumor gastric tissues. We used siRNA gene silencing, in BGC-823 gastric cancer cell lines, to target adrenomedullin genes, and found that increased adrenomedullin expression results in the proliferation of tumor cells, tumor invasion, and metastasis...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733542/use-of-a-genome-wide-haploid-genetic-screen-to-identify-treatment-predicting-factors-a-proof-of-principle-study-in-pancreatic-cancer
#17
Yuk Ting Ma, Sarah M Leonard, Naheema Gordon, Jennifer Anderton, Claire James, David Huen, Ciaran B Woodman, Daniel H Palmer
The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#18
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#19
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#20
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
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