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Casein kinase 1

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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
#1
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...
June 21, 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
#2
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...
June 10, 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
#3
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 [3H]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 non-specific binding...
June 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating
#4
Lisa R Goldberg, Stacey L Kirkpatrick, Neema Yazdani, Kimberly P Luttik, Olga A Lacki, R Keith Babbs, David F Jenkins, W Evan Johnson, Camron 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
#5
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
#6
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
#7
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...
May 15, 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
#8
Mary C Horne, Johannes W Hell
Ca(2+) influx via the L-type Ca(2+) channel Cav 1.2 triggers our heartbeat. Perinatally and particularly at birth, angiotensin II is produced to augment necessary physiological changes in blood flow such as pulmonary perfusion. This article is protected by copyright. All rights reserved.
May 9, 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
#9
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
#10
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-hyper-phosphorylation-site-responsible-for-hcv-replication
#11
Shih-Chin Hsu, Chieh-Wen Lo, Ting-Chun Pan, Kuan-Ying Lee, Ming-Jiun Yu
The non-structural protein 5A (NS5A) of the hepatitis C virus (HCV) is a phosphoprotein with two phosphorylation states: hypo- and hyper-phosphorylation. Genetic mutation studies have demonstrated a cluster of serine residues responsible for NS5A hyper-phosphorylation 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...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28402261/association-of-ckip-1-p21a-polymorphism-with-risk-of-chronic-heart-failure-in-a-chinese-population
#15
Mu-Peng Li, Yan-Jiao Zhang, Xiao-Lei Hu, Ji-Peng Zhou, Yong-Long Yang, Li-Ming Peng, Hong Qi, Tian-Lun Yang, Xiao-Ping Chen
Pathological cardiac hypertrophy is an independent risk factor for chronic heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) can inhibit pathological cardiac hypertrophy. Therefore, we investigated whether CKIP-1 nonsynonymous polymorphism rs2306235 (Pro21Ala) contributes to risk and prognosis of chronic heart failure in a Chinese population.A total of 923 adult patients with chronic heart failure and 1020 age- and gender-matched healthy controls were recruited. CKIP-1 rs2306235 polymorphism was genotyped using PCR-restriction fragment length polymorphism...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28380520/the-addition-of-protein-bound-amino-acids-in-low-protein-diets-improves-the-metabolic-and-immunological-characteristics-in-fifteen-to-thirty-five-kg-pigs
#16
L Q Che, X Peng, L Hu, C Wu, Q Xu, Z F Fang, Y Lin, S Y Xu, J Li, B Feng, G Tian, R N Zhang, H Sun, D Wu, D W Chen
This study was to evaluate the effects of supplementation of AA form (crystalline vs. protein bound) in low-protein diets on growth, metabolic, and immunological characteristics of pigs. A total of 80 barrows (PIC 327 × 1050; 15.57 ± 0.13 kg BW and 48 ± 2 d of age), housed in 4 pigs per pen with 5 pens per treatment, were assigned to 4 dietary treatments of 17, 15, and 13% CP and 13% CP plus casein for 28 d. The crystalline AA were supplemented to meet the requirement of indispensable AA in pigs. Results showed that pigs fed the 13% CP diet or the 13% CP plus casein diet had lower ( < 0...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28355568/a-sequentially-priming-phosphorylation-cascade-activates-the-gliomagenic-transcription-factor-olig2
#17
Jing Zhou, An-Chi Tien, John A Alberta, Scott B Ficarro, Amelie Griveau, Yu Sun, Janhavee S Deshpande, Joseph D Card, Meghan Morgan-Smith, Wojciech Michowski, Rintaro Hashizume, C David James, Keith L Ligon, William D Snider, Peter Sicinski, Jarrod A Marto, David H Rowitch, Charles D Stiles
During development of the vertebrate CNS, the basic helix-loop-helix (bHLH) transcription factor Olig2 sustains replication competence of progenitor cells that give rise to neurons and oligodendrocytes. A pathological counterpart of this developmental function is seen in human glioma, wherein Olig2 is required for maintenance of stem-like cells that drive tumor growth. The mitogenic/gliomagenic functions of Olig2 are regulated by phosphorylation of a triple serine motif (S10, S13, and S14) in the amino terminus...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28351752/deficiency-of-ckip-1-aggravates-high-fat-diet-induced-fatty-liver-in-mice
#18
Yutao Zhan, Ping Xie, Dongnian Li, Li Li, Jing Chen, Wei An, Lingqiang Zhang, Chuan Zhang
Casein kinase 2 interacting protein-1(CKIP-1) is widely expressed in a variety of tissues and cells, and plays an important role in various critical cellular and physiological processes including cell growth, apoptosis, differentiation, cytoskeleton and bone formation. Here, we found: (1) CKIP-1 deficient mice exhibited increased body weight, liver weight, number and size of lipid droplets, and TG content comparing with WT mice after being exposed to high fat diet (HFD); (2) the levels of serum insulin, liver glycogen, phosphorylated C-Jun-N-terminal kinase-1 (pJNK1) and phosphorylated insulin receptor substrate -1(pIRS1) in CKIP-1(-/-) mice were higher than those of WT mice; (3) CKIP-1 interacted with JNK1 in vitro...
March 27, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28348572/a-casein-kinase-ii-phosphorylation-site-in-atyy1-affects-its-activity-stability-and-function-in-the-aba-response
#19
Xiu-Yun Wu, Tian Li
The phosphorylation and dephosphorylation of proteins are crucial in the regulation of protein activity and stability in various signaling pathways. In this study, we identified an ABA repressor, Arabidopsis Ying Yang 1 (AtYY1) as a potential target of casein kinase II (CKII). AtYY1 physically interacts with two regulatory subunits of CKII, CKB3, and CKB4. Moreover, AtYY1 can be phosphorylated by CKII in vitro, and the S(284) site is the major CKII phosphorylation site. Further analyses indicated that S(284) phosphorylation can enhance the transcriptional activity and protein stability of AtYY1 and hence strengthen the effect of AtYY1 as a negative regulator in the ABA response...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28344765/new-insights-on-thyroid-hormone-mediated-regulation-of-herpesvirus-infections
#20
REVIEW
Robert W Figliozzi, Feng Chen, S Victor Hsia
Thyroid hormone (T3) has been suggested to participate in the regulation of herpesvirus replication during reactivation. Clinical observations and in vivo experiments suggest that T3 are involved in the suppression of herpes virus replication. In vitro, differentiated LNCaP cells, a human neuron-like cells, further resisted HSV-1 replication upon addition of T3. Previous studies indicate that T3 controlled the expression of several key viral genes via its nuclear receptors in differentiated LNCaP cells. Additional observation showed that differentiated LNCaP cells have active PI3K signaling and inhibitor LY294002 can reverse T3-mediated repression of viral replication...
2017: Cell & Bioscience
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