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Ck2 casein kinase

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https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#1
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29021227/physiological-regulation-of-the-epithelial-na-channel-by-casein-kinase-ii
#2
Jonathan M Berman, Elena Mironova, James D Stockand
The Epithelial Na+ Channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine-tuning of electrolyte and water excretion and consequently, blood pressure. Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary for normal ENaC activity. We tested the physiological importance of CK2 regulation of ENaC as the degree to which ENaC activity is dependent on CK2 phosphorylation in the living organism is unknown...
October 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29021214/casein-kinase-ii-phosphorylation-of-cyclin-f-at-serine-621-regulates-the-lys48-ubiquitylation-e3-ligase-activity-of-the-scf-cyclin-f-complex
#3
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
https://www.readbyqxmd.com/read/28994305/plant-homeodomain-finger-protein-2-as-a-novel-ikaros-target-in-acute-lymphoblastic-leukemia
#4
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
AIM: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. METHODS: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. RESULTS: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 (low) expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL...
October 10, 2017: Epigenomics
https://www.readbyqxmd.com/read/28992316/phosphorylation-of-cbx2-controls-its-nucleosome-binding-specificity
#5
Takayuki Kawaguchi, Shinichi Machida, Hitoshi Kurumizaka, Hideaki Tagami, Jun-Ichi Nakayama
Chromobox 2 (CBX2), a component of polycomb repressive complex 1 (PRC1), binds lysine 27-methylated histone H3 (H3K27me3) via its chromodomain (CD) and plays a critical role in repressing developmentally regulated genes. The phosphorylation of CBX2 has been described in several studies, but the biological implications of this modification remain largely elusive. Here, we show that CBX2's phosphorylation plays an important role in its nucleosome binding. CBX2 is stably phosphorylated in vivo, and domain analysis showed that residues in CBX2's serine-rich (SR) region are the predominant phosphorylation sites...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28939766/casein-kinase-2-mediated-phosphorylation-of-brahma-related-gene-1-controls-myoblast-proliferation-and-contributes-to-swi-snf-complex-composition
#6
Teresita Padilla-Benavides, Brian T Nasipak, Amanda L Paskavitz, Dominic T Haokip, Jake M Schnabl, Jeffrey A Nickerson, Anthony N Imbalzano
Transcriptional regulation is modulated in part by chromatin remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCβ1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928125/ck2%C3%AE-critically-regulates-thrombopoiesis-and-ca-2-triggered-platelet-activation-in-arterial-thrombosis-in-vivo
#7
Patrick Münzer, Britta Walker-Allgaier, Sascha Geue, Friederike Langhauser, Eva Geuss, David Stegner, Katja Aurbach, Daniela Semeniak, Madhumita Chatterjee, Irene Gonzalez Menendez, Melanie Märklin, Leticia Quintanilla-Martinez, Helmut R Salih, David W Litchfield, Thierry Buchou, Christoph Kleinschnitz, Florian Lang, Bernhard Nieswandt, Irina Pleines, Harald Schulze, Meinrad Gawaz, Oliver Borst
Platelets, anucleated megakaryocyte-derived cells, play a major role in hemostasis and arterial thrombosis. While protein kinase Casein Kinase 2 (CK2) is readily detected in megakaryocytes and platelets, the impact of CK2-dependent signaling on megakaryocyte/platelet (patho-) physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. Megakaryocyte/platelet-specific genetic deletion of CK2β (ck2β(-/-) ) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with enhanced proportion of premature platelets...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28883547/casein-kinase-2-is-a-critical-determinant-of-the-balance-of-th17-and-treg-cell-differentiation
#8
Sung Woong Jang, Soo Seok Hwang, Hyeong Su Kim, Keoung Oh Lee, Min Kyung Kim, Wonyong Lee, Kiwan Kim, Gap Ryol Lee
Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro...
September 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28873435/tgf-%C3%AE-signaling-is-an-effective-target-to-impair-survival-and-induce-apoptosis-of-human-cholangiocarcinoma-cells-a-study-on-human-primary-cell-cultures
#9
Anna Maria Lustri, Sabina Di Matteo, Alice Fraveto, Daniele Costantini, Alfredo Cantafora, Chiara Napoletano, Maria Consiglia Bragazzi, Felice Giuliante, Agostino M De Rose, Pasquale B Berloco, Gian Luca Grazi, Guido Carpino, Domenico Alvaro
Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT...
2017: PloS One
https://www.readbyqxmd.com/read/28798693/phosphorylation-modulates-ameloblastin-self-assembly-and-ca-2-binding
#10
Øystein Stakkestad, Ståle P Lyngstadaas, Bernd Thiede, Jiri Vondrasek, Bjørn S Skålhegg, Janne E Reseland
Ameloblastin (AMBN), an important component of the self-assembled enamel extra cellular matrix, contains several in silico predicted phosphorylation sites. However, to what extent these sites actually are phosphorylated and the possible effects of such post-translational modifications are still largely unknown. Here we report on in vitro experiments aimed at investigating what sites in AMBN are phosphorylated by casein kinase 2 (CK2) and protein kinase A (PKA) and the impact such phosphorylation has on self-assembly and calcium binding...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28748912/a-novel-allosteric-site-in-casein-kinase-2%C3%AE-discovered-using-combining-bioinformatics-and-biochemistry-methods
#11
Hai-Ming Jiang, Jiang-Kai Dong, Kun Song, Tong-Dan Wang, Wen-Kang Huang, Jing-Miao Zhang, Xiu-Yan Yang, Ying Shen, Jian Zhang
Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28698370/g9a-coordinates-with-the-rpa-complex-to-promote-dna-damage-repair-and-cell-survival
#12
Qiaoyan Yang, Qian Zhu, Xiaopeng Lu, Yipeng Du, Linlin Cao, Changchun Shen, Tianyun Hou, Meiting Li, Zhiming Li, Chaohua Liu, Di Wu, Xingzhi Xu, Lina Wang, Haiying Wang, Ying Zhao, Yang Yang, Wei-Guo Zhu
Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28683323/identification-of-a-druggable-pathway-controlling-glioblastoma-invasiveness
#13
Nora Pencheva, Mark C de Gooijer, Daniel J Vis, Lodewyk F A Wessels, Tom Würdinger, Olaf van Tellingen, René Bernards
Diffuse and uncontrollable brain invasion is a hallmark of glioblastoma (GBM), but its mechanism is understood poorly. We developed a 3D ex vivo organotypic model to study GBM invasion. We demonstrate that invading GBM cells upregulate a network of extracellular matrix (ECM) components, including multiple collagens, whose expression correlates strongly with grade and clinical outcome. We identify interferon regulatory factor 3 (IRF3) as a transcriptional repressor of ECM factors and show that IRF3 acts as a suppressor of GBM invasion...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28672764/interaction-of-tubulin-and-protein-kinase-ck2-in-trypanosoma-equiperdum
#14
Beatriz E Boscán, Graciela L Uzcanga, Maritza Calabokis, Rocío Camargo, Frank Aponte, José Bubis
A polypeptide band with an apparent molecular weight of 55,000 was phosphorylated in vitro in whole-cell lysates of Trypanosoma equiperdum. This band corresponds to tubulin as demonstrated by immunoprecipitation of the phosphorylated polypeptide from T. equiperdum extracts when anti-α and anti-β tubulin monoclonal antibodies were employed. A parasite protein kinase CK2 was in charge of modifying tubulin given that common mammalian CK2 inhibitors such as emodin and GTP, hindered the phosphorylation of tubulin and exogenously added casein...
June 27, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28623166/casein-kinase-ii-ck2-glycogen-synthase-kinase-3-gsk-3-and-ikaros-mediated-regulation-of-leukemia
#15
REVIEW
Chandrika Gowda, Mario Soliman, Malika Kapadia, Yali Ding, Kimberly Payne, Sinisa Dovat
Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN...
June 13, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28585349/csnk2b-splice-site-mutations-in-patients-cause-intellectual-disability-with-or-without-myoclonic-epilepsy
#16
Karine Poirier, Laurence Hubert, Géraldine Viot, Marlène Rio, Pierre Billuart, Claude Besmond, Thierry Bienvenu
De novo mutations are a frequent cause of disorders related to brain development. We report the results from the screening of two patients diagnosed with intellectual disability (ID) using exome sequencing to identify new causative de novo mutations. Exome sequencing was conducted in two patient-parent trios to identify de novo variants. In silico and expression studies were also performed to evaluate the functional consequences of these variants. The two patients presented developmental delay with minor facial dysmorphy...
August 2017: Human Mutation
https://www.readbyqxmd.com/read/28533810/tc003132-is-essential-for-the-follicle-stem-cell-lineage-in-telotrophic-tribolium-oogenesis
#17
Matthias Teuscher, Nadi Ströhlein, Markus Birkenbach, Dorothea Schultheis, Michael Schoppmeier
BACKGROUND: Stem cells are undifferentiated cells with a potential for self-renewal, which are essential to support normal development and homeostasis. To gain insight into the molecular mechanisms underlying adult stem cell biology and organ evolution, we use the telotrophic ovary of the beetle Tribolium. To this end, we participated in a large-scale RNAi screen in the red flour beetle Tribolium, which identified functions in embryonic and postembryonic development for more than half of the Tribolium genes...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28533219/obesity-linked-phosphorylation-of-sirt1-by-casein-kinase-2-inhibits-its-nuclear-localization-and-promotes-fatty-liver
#18
Sung E Choi, Sanghoon Kwon, Sunmi Seok, Zhen Xiao, Kwan-Woo Lee, Yup Kang, Xiaoling Li, Kosaku Shinoda, Shingo Kajimura, Byron Kemper, Jongsook Kim Kemper
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity...
August 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28495796/phosphorylation-of-nhe3-s-719-regulates-nhe3-activity-through-the-formation-of-multiple-signaling-complexes
#19
Rafiquel Sarker, Boyoung Cha, Olga Kovbasnjuk, Robert Cole, Sandra Gabelli, Chung Ming Tse, Mark Donowitz
Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a downstream site (S719) that accounts for 40% of basal NHE3 activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further examined by mutation of NHE3-S(719) to A (not phosphorylated) or D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3 activity: 1) reduced basal NHE3 activity-specifically, inhibition of the PI3K/AKT-dependent component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation; and 3) reduced acute inhibition of NHE3 activity-specifically, elevated Ca(2+) related (carbachol/Ca(2+) ionophore), but there was normal inhibition by forskolin and hyperosmolarity...
July 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#20
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
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