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Casein kinase 1

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https://www.readbyqxmd.com/read/28793293/triggering-of-eryptosis-the-suicidal-erythrocyte-death-by-mammalian-target-of-rapamycin-mtor-inhibitor-temsirolimus
#1
Abdulla Al Mamun Bhuyan, Hang Cao, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is utilized for the treatment of malignancy. Temsirolimus is at least in part effective by triggering suicidal tumor cell death. The most common side effect of temsirolimus treatment is anemia. At least in theory, the anemia following temsirolimus treatment could result from stimulation of eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28791381/protective-effect-of-diminazene-attenuates-myocardial-infarction-in-rats-via-increased-inflammation-and-ace2-activity
#2
Junjiang Chen, Lianqun Cui, Jingliang Yuan, Songcun Zhang, Rongmei Ma, Hongjun Sang, Qingjiang Liu, Lianfeng Shan
The present study aimed to investigate whether diminazene attenuates myocardial infarction (MI) in rats. In addition, the present study investigated whether ACE2 signaling was involved in the effects of diminazene on protein function. A rat model of acute myocardial infarction (AMI) was established by occlusion of the left anterior descending coronary artery. The AMI model rats received intraperitoneal injections of diminazene (5 mg/kg/day) for 3 days. Treatment with diminazene significantly inhibited the expression of casein kinase and lactate dehydrogenase, and reduced infarct size in AMI rats...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28720768/gilgamesh-is-required-for-the-maintenance-of-germline-stem-cells-in-drosophila-testis
#3
Dongsheng Chen, Xiangxiang Zhu, Lijuan Zhou, Jian Wang, Xiaoqian Tao, Shuang Wang, Fuling Sun, Xianzhao Kan, Zhengqi Han, Yuelin Gu
Emerging evidence supports that stem cells are regulated by both intrinsic and extrinsic mechanisms. However, factors that determine the fate of stem cells remain incompletely understood. The Drosophila testis provides an exclusive powerful model in searching for potential important regulatory factors and their underlying mechanisms for controlling the fate of germline stem cells (GSCs). In this study, we have found that Drosophila gilgamesh (gish), which encodes a homologue of human CK1-γ (casein kinase 1-gamma), is required intrinsically for GSC maintenance...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701347/a-casein-kinase-1-prevents-expulsion-of-the-oocyte-meiotic-spindle-into-a-polar-body-by-regulating-cortical-contractility
#4
Jonathan R Flynn, Francis J McNally
During female meiosis, haploid eggs are generated from diploid oocytes. This reduction in chromosome number occurs through two highly asymmetric cell divisions resulting in one large egg and two small polar bodies. Unlike mitosis, where an actomyosin contractile ring forms between the sets of segregating chromosomes, the meiotic contractile ring forms on the cortex adjacent to one spindle pole, then ingresses down the length of the spindle to position itself at the exact midpoint between the two sets of segregating chromosomes...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28678581/downregulation-of-the-ifnar1-chain-of-type-1-interferon-receptor-contributes-to-the-maintenance-of-the-haematopoietic-stem-cells
#5
Jun Gui, Bin Zhao, Kaosheng Lyu, Wei Tong, Serge Y Fuchs
Recent studies demonstrated that prolonged exposure of haematopoietic stem cells (HSCs) to type I interferons (IFN) stimulates HSCs entrance into cell cycle, continuous proliferation and eventual exhaustion, which could be prevented by ablation of the Ifnar1 chain of IFN receptor. Given that levels IFNAR1 expression can be robustly affected by IFN-independent ubiquitination and downregulation of IFNAR1 in response to activation of protein kinases such as protein kinase R-like endoplasmic reticulum kinase (PERK) and casein kinase 1α (CK1α), we aimed to determine the role of IFNAR1 downregulation in the maintenance of HSCs...
July 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28647331/combination-of-histidine-lysine-methionine-and-leucine-promotes-%C3%AE-casein-synthesis-via-the-mechanistic-target-of-rapamycin-signaling-pathway-in-bovine-mammary-epithelial-cells
#6
H N Gao, S G Zhao, N Zheng, Y D Zhang, S S Wang, X Q Zhou, J Q Wang
The ratio of different AA in the diets of cows is vital to improve milk protein yield. β-Casein is one of the important milk proteins with high nutritive value. However, the suitable ratio of essential amino acids (EAA) for the expression of β-casein in the immortalized bovine mammary epithelial cell line is not fully characterized. This study employed response surface methodology to determine the optimal ratio of His, Lys, Met, and Leu on β-casein expression level in vitro and clarified the effect of the 4 EAA on β-casein via the mechanistic target of rapamycin (mTOR) signaling pathway...
September 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28636034/upregulation-of-heme-oxygenase-1-mediates-the-anti-inflammatory-activity-of-casein-glycomacropeptide-gmp-hydrolysates-in-lps-stimulated-macrophages
#7
Tiange Li, Xue Cheng, Min Du, Bin Chen, Xueying Mao
Recently, we have shown that casein glycomacropeptide hydrolysates (GHP) exhibit both anti-inflammatory and anti-oxidative activities in vitro. However, whether heme oxygenase-1 (HO-1) is involved in the cytoprotective effect of GHP against the inflammatory status remains unclear. Therefore, we hypothesized that HO-1 is a potential target of GHP, which mediates its anti-inflammatory effect. Here, GHP inhibited the intracellular reactive oxygen species (ROS) accumulation and NADPH oxidase 2 (NOX2) expression and enhanced reduced glutathione (GSH) levels in LPS-stimulated RAW264...
July 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28620137/biological-specificity-of-cdk4-6-inhibitors-dose-response-relationship-in-vivo-signaling-and-composite-response-signature
#8
Erik S Knudsen, Jack Hutcheson, Paris Vail, Agnieszka K Witkiewicz
Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609096/identification-and-profiling-of-a-selective-and-brain-penetrant-radioligand-for-in-vivo-target-occupancy-measurement-of-casein-kinase-1-ck1-inhibitors
#9
Travis T Wager, Paul Galatsis, Ramalakshmi Y Chandrasekaran, Todd W Butler, Jianke Li, Lei Zhang, Scot Mente, Chakrapani Subramanyam, Shenping Liu, Angela C Doran, Cheng Chang, Katherine Fisher, Sarah Grimwood, Joseph R Hedde, Michael Marconi, Klaas Schildknegt
To enable the clinical development of our CNS casein kinase 1 delta/epsilon (CK1δ/ε) inhibitor project, we investigated the possibility of developing a CNS positron emission tomography (PET) radioligand. For this effort, we focused our design and synthesis efforts on the initial CK1δ/ε inhibitor HTS hits with the goal of identifying a compound that would fulfill a set of recommended PET ligand criteria. We identified [(3)H]PF-5236216 (9) as a tool ligand that meets most of the key CNS PET attributes including high CNS MPO PET desirability score and kinase selectivity, CNS penetration, and low nonspecific binding...
June 30, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating1
#10
L R Goldberg, S L Kirkpatrick, N Yazdani, K P Luttik, O A Lacki, R Keith Babbs, D F Jenkins, W Evan Johnson, C D Bryant
Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28571942/corrigendum-to-interaction-of-casein-kinase-1-delta-ck1-delta-with-the-light-chain-lc2-of-microtubule-associated-protein-1a-map1a-biochim-biophys-acta-1745-2-2005-196-2006
#11
Sonja Wolff, Zhenyu Xiao, Mathias Wittau, Nadine Süssner, Martin Stöter, Uwe Knippschild
No abstract text is available yet for this article.
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28545154/site-specific-phosphorylation-of-casein-kinase-1-%C3%AE-ck1%C3%AE-regulates-its-activity-towards-the-circadian-regulator-per2
#12
Gracie Wee Ling Eng, Edison, David M Virshup
Circadian rhythms are intrinsic ~24 hour cycles that regulate diverse aspects of physiology, and in turn are regulated by interactions with the external environment. Casein kinase 1 delta (CK1δ, CSNK1D) is a key regulator of the clock, phosphorylating both stabilizing and destabilizing sites on the PER2 protein, in a mechanism known as the phosphoswitch. CK1δ can itself be regulated by phosphorylation on its regulatory domain, but the specific sites involved, and the role this plays in control of circadian rhythms as well as other CK1-dependent processes is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#13
Wei-Chun J Hsu, Norelle C 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, Jay S 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...
September 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28488737/angiotensin-ii-signalling-kicks-out-p27-kip1-casein-kinase-2-augmentation-of-cav-1-2-l-type-ca-2-channel-activity-in-immature-ventricular-cardiomyocytes
#14
Mary C Horne, Johannes W Hell
No abstract text is available yet for this article.
July 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28487075/n-1h-pyrazol-3-yl-quinazolin-4-amines-as-a-novel-class-of-casein-kinase-1%C3%AE-%C3%AE%C2%B5-inhibitors-synthesis-biological-evaluation-and-molecular-modeling-studies
#15
Chandrabose Karthikeyan, Pramod Jharia, Digambar Kumar Waiker, Amy Catherine Nusbaum, Haneen Amawi, Erin Marie Kirwen, Ryann Christman, Sri Krishna Chaitanya Arudra, Laurent Meijer, Amit K Tiwari, Piyush Trivedi
Described herein is the design, synthesis and biological evaluation of a series of N-(1H-pyrazol-3-yl)quinazolin-4-amines against a panel of eight disease relevant protein kinases. The kinase inhibition results indicated that two compounds inhibited casein kinase 1δ/ε (CK1δ/ε) with some selectivity over related kinases, namely CDK5/p25, GSK-3α/β, and DYRK1A. Docking studies with 3c and 3d revealed the key interactions with desired amino acids in the ATP binding site of CK1δ. Furthermore, compound 3c also elicited selective cytotoxic activity against the pancreas ductal adenocarcinoma (PANC-1) cell line...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28446880/shifts-in-the-gut-microbiota-composition-due-to-depleted-bone-marrow-beta-adrenergic-signaling-are-associated-with-suppressed-inflammatory-transcriptional-networks-in-the-mouse-colon
#16
Tao Yang, Niousha Ahmari, Jordan T Schmidt, Ty Redler, Rebeca Arocha, Kevin Pacholec, Kacy L Magee, Wendi Malphurs, Jennifer L Owen, Gregory A Krane, Eric Li, Gary P Wang, Thomas W Vickroy, Mohan K Raizada, Christopher J Martyniuk, Jasenka Zubcevic
The brain-gut axis plays a critical role in the regulation of different diseases, many of which are characterized by sympathetic dysregulation. However, a direct link between sympathetic dysregulation and gut dysbiosis remains to be illustrated. Bone marrow (BM)-derived immune cells continuously interact with the gut microbiota to maintain homeostasis in the host. Their function is largely dependent upon the sympathetic nervous system acting via adrenergic receptors present on the BM immune cells. In this study, we utilized a novel chimera mouse that lacks the expression of BM beta1/2 adrenergic receptors (b1/2-ARs) to investigate the role of the sympathetic drive to the BM in gut and microbiota homeostasis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446668/serine-235-is-the-primary-ns5a-hyperphosphorylation-site-responsible-for-hepatitis-c-virus-replication
#17
Shih-Chin Hsu, Chieh-Wen Lo, Ting-Chun Pan, Kuan-Ying Lee, Ming-Jiun Yu
The nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) is a phosphoprotein with two phosphorylation states: hypo- and hyperphosphorylation. Genetic mutation studies have demonstrated a cluster of serine residues responsible for NS5A hyperphosphorylation and functions in viral replication and assembly; however, the phosphorylation levels and potential interactions among the serine residues are unclear. We used three specific antibodies to measure NS5A phosphorylation at S222, S235, and S238 that were identified in our previous proteomics study...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#18
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28412246/absence-of-nucks-augments-paracrine-effects-of-mesenchymal-stem-cells-mediated-cardiac-protection
#19
Yuelin Zhang, Sinming Chiu, Xiaoting Liang, Yuet-Hung Chai, Yiming Qin, Junwen Wang, Xiang Li, Beiying Qiu, Vinay Tergaonkar, Hung-Fat Tse, Qizhou Lian
Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial repair after myocardial infarction (MI) by secreting a panel of growth factors and cytokines. This study was to investigate the potential mechanisms of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in regulation of the profiles of BM-MSCs secretion and compare the therapeutic efficacy of NUCKS(-/-)- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion profiles between NUCKS(-/-)- and WT-BM-MSCs under hypoxia (1%O2) were analyzed...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28404913/a-novel-role-of-ckip-1-in-promoting-megakaryocytic-differentiation
#20
Jiao Fan, Yiwu Wang, Yuan Shen, Qingyan Liu, Rong Gao, Ya Qiu, Chanjuan Wang, Lingqiang Zhang
Casein kinase 2-interacting protein-1 (CKIP-1) is a known regulator of cardiomyocytes and macrophage proliferation. In this study, we showed that CKIP-1 was involved in the process of megakaryocytic differentiation. During megakaryocytic differentiation of K562 cells, CKIP-1 was dramatically upregulated and this upregulation induced by PMA was mediated through downregulation of transcription factor GATA-1. By transient transfection, oligonucleotide-directed mutagenesis and chromatin immunoprecipitation assays, we identified the transcriptional regulation of CKIP-1 by GATA-1...
May 2, 2017: Oncotarget
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