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Artículos de revistas sobre el tema "Dark kinase"

Autor: Grafiati

Publicado: 6 de enero de 2025

Última modificación: 31 de julio de 2025

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1

Plutzer, Isaac, Dhaval P. Bhatt, Emily M. Wilkerson, Regan Williamson, Dennis Goldfarb, and M. Ben Major. "Abstract 4126: Illuminating the dark kinome using proximity labeling and phosphoproteomics analysis." Cancer Research 85, no. 8_Supplement_1 (2025): 4126. https://doi.org/10.1158/1538-7445.am2025-4126.

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Kinases are highly druggable targets for cancer therapy due to their control over a variety of oncogenic processes via protein phosphorylation. While, large clinical phosphoproteomics datasets have expanded our understanding of how the phosphoproteome is altered in cancer, annotation of the phosphoproteome is significantly lacking. 95% of phosphorylation sites in the PhosphoSitePlus database have no associated kinase, and 80% of annotated substrates are assigned to just 20% of the most well-studied kinases. Of the ∼650 kinases in the human genome, 162 are designated by the NIH as ‘dark kinases

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2

Soleymani, Saber, Nathan Gravel, Liang-Chin Huang, et al. "Dark kinase annotation, mining, and visualization using the Protein Kinase Ontology." PeerJ 11 (December 5, 2023): e16087. http://dx.doi.org/10.7717/peerj.16087.

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The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships among protein kinase sequence, structure, function, and disease in a human and machine-readable format. In this study, we have significantly expanded ProKinO by incorporating additional data on expression patterns and drug interactions. Furthermore, we have developed a completely new browser from the ground up to render the knowledge graph visible and interactive on the web. We have enriched ProKinO with new classes and relationships that capture information on kinase ligand bin

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3

Needham, Elise J., Benjamin L. Parker, Timur Burykin, David E. James, and Sean J. Humphrey. "Illuminating the dark phosphoproteome." Science Signaling 12, no. 565 (2019): eaau8645. http://dx.doi.org/10.1126/scisignal.aau8645.

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Protein phosphorylation is a major regulator of protein function and biological outcomes. This was first recognized through functional biochemical experiments, and in the past decade, major technological advances in mass spectrometry have enabled the study of protein phosphorylation on a global scale. This rapidly growing field of phosphoproteomics has revealed that more than 100,000 distinct phosphorylation events occur in human cells, which likely affect the function of every protein. Phosphoproteomics has improved the understanding of the function of even the most well-characterized protein

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4

Sawyers, Charles L. "Will Kinase Inhibitors Have a Dark Side?" New England Journal of Medicine 355, no. 3 (2006): 313–15. http://dx.doi.org/10.1056/nejmcibr062354.

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5

Southekal, Siddesh, Nitish Kumar Mishra, and Chittibabu Guda. "Pan-Cancer Analysis of Human Kinome Gene Expression and Promoter DNA Methylation Identifies Dark Kinase Biomarkers in Multiple Cancers." Cancers 13, no. 6 (2021): 1189. http://dx.doi.org/10.3390/cancers13061189.

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Kinases are a group of intracellular signaling molecules that play critical roles in various biological processes. Even though kinases comprise one of the most well-known therapeutic targets, many have been understudied and therefore warrant further investigation. DNA methylation is one of the key epigenetic regulators that modulate gene expression. In this study, the human kinome’s DNA methylation and gene expression patterns were analyzed using the level-3 TCGA data for 32 cancers. Unsupervised clustering based on kinome data revealed the grouping of cancers based on their organ level and ti

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6

Berginski, Matthew E., Nienke Moret, Changchang Liu, Dennis Goldfarb, Peter K. Sorger, and Shawn M. Gomez. "The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases." Nucleic Acids Research 49, no. D1 (2020): D529—D535. http://dx.doi.org/10.1093/nar/gkaa853.

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Abstract Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these

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7

Anandakrishnan, Manju, Karen E. Ross, Chuming Chen, Vijay Shanker, Julie Cowart, and Cathy H. Wu. "KSFinder—a knowledge graph model for link prediction of novel phosphorylated substrates of kinases." PeerJ 11 (October 6, 2023): e16164. http://dx.doi.org/10.7717/peerj.16164.

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Background Aberrant protein kinase regulation leading to abnormal substrate phosphorylation is associated with several human diseases. Despite the promise of therapies targeting kinases, many human kinases remain understudied. Most existing computational tools predicting phosphorylation cover less than 50% of known human kinases. They utilize local feature selection based on protein sequences, motifs, domains, structures, and/or functions, and do not consider the heterogeneous relationships of the proteins. In this work, we present KSFinder, a tool that predicts kinase-substrate links by captu

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8

Cozza, G., F. Meggio, and S. Moro. "The Dark Side of Protein Kinase CK2 Inhibition." Current Medicinal Chemistry 18, no. 19 (2011): 2867–84. http://dx.doi.org/10.2174/092986711796150423.

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9

Salcedo, Mariah V., Nathan Gravel, Abbas Keshavarzi, Liang-Chin Huang, Krzysztof J. Kochut, and Natarajan Kannan. "Predicting protein and pathway associations for understudied dark kinases using pattern-constrained knowledge graph embedding." PeerJ 11 (October 18, 2023): e15815. http://dx.doi.org/10.7717/peerj.15815.

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The 534 protein kinases encoded in the human genome constitute a large druggable class of proteins that include both well-studied and understudied “dark” members. Accurate prediction of dark kinase functions is a major bioinformatics challenge. Here, we employ a graph mining approach that uses the evolutionary and functional context encoded in knowledge graphs (KGs) to predict protein and pathway associations for understudied kinases. We propose a new scalable graph embedding approach, RegPattern2Vec, which employs regular pattern constrained random walks to sample diverse aspects of node cont

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10

Weiss, Ellen. "Shedding light on dark adaptation." Biochemist 42, no. 5 (2020): 44–50. http://dx.doi.org/10.1042/bio20200067.

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The retina is famous for its ability to operate under a broad range of light intensities. This is partly due to the presence of two types of photoreceptor cells, rods and cones. Rods are used mostly for dim light vision, and cones are used for bright light and colour vision. These cells are also able to adapt to a broad range of light intensities using light- and dark-adaptation mechanisms. Dark adaptation is used by the vertebrate retina to increase its visual sensitivity when moving from a brightly lit environment to a dark environment. The brighter the surrounding light, the longer it takes

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11

Jiang, Wen, Eric Jaehnig, and Bing Zhang. "Abstract 2023: CoPheeMap: a co-regulation map of 30,000 phosphosite illuminates the dark cancer phosphoproteome." Cancer Research 83, no. 7_Supplement (2023): 2023. http://dx.doi.org/10.1158/1538-7445.am2023-2023.

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Abstract Mass spectrometry-based phosphoproteomics enables proteome-wide analysis of protein phosphorylation in biological samples. As a prime example, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has performed phosphoproteomic profiling for 1,191 tumors spanning 11 cancer types, generating quantitative data on 77,442 phosphosites. Despite the impressive data generation power, only less than 5% of these phosphosites have been associated with a regulatory kinase or biological function, and 90% of these annotated phosphosites were associated with 20% well-studied kinases. The “dark”

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12

Lee, Horim. "Mitogen-Activated Protein Kinase Kinase 3 Is Required for Regulation during Dark-Light Transition." Molecules and Cells 38, no. 7 (2015): 651–56. http://dx.doi.org/10.14348/molcells.2015.0055.

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13

Shen, Shensi, and Zhen Tan. "Illuminating a Dark Kinase in the Mesenchymal Cancer Cell State." Cancer Discovery 15, no. 3 (2025): 458–60. https://doi.org/10.1158/2159-8290.cd-24-1884.

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Summary: Killarney and colleagues identify PKN2 as a critical driver of mesenchymal cancer cell survival and drug resistance through YAP/TAZ activation. Targeting PKN2 in combination with first-line targeted therapies offers a potential strategy to eliminate mesenchymal-like drug-tolerant persister cells. See related article by Killarney et al., p. 595

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14

Deznabi, Iman, Busra Arabaci, Mehmet Koyutürk, and Oznur Tastan. "DeepKinZero: zero-shot learning for predicting kinase–phosphosite associations involving understudied kinases." Bioinformatics 36, no. 12 (2020): 3652–61. http://dx.doi.org/10.1093/bioinformatics/btaa013.

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Abstract Motivation Protein phosphorylation is a key regulator of protein function in signal transduction pathways. Kinases are the enzymes that catalyze the phosphorylation of other proteins in a target-specific manner. The dysregulation of phosphorylation is associated with many diseases including cancer. Although the advances in phosphoproteomics enable the identification of phosphosites at the proteome level, most of the phosphoproteome is still in the dark: more than 95% of the reported human phosphosites have no known kinases. Determining which kinase is responsible for phosphorylating a

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15

Hao, Yuhan, Haijiao Wang, Shenglong Qiao, Linna Leng, and Xuelu Wang. "Histone deacetylase HDA6 enhances brassinosteroid signaling by inhibiting the BIN2 kinase." Proceedings of the National Academy of Sciences 113, no. 37 (2016): 10418–23. http://dx.doi.org/10.1073/pnas.1521363113.

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Glycogen synthase kinase 3 (GSK3)-like kinases play important roles in brassinosteroid (BR), abscisic acid, and auxin signaling to regulate many aspects of plant development and stress responses. The Arabidopsis thaliana GSK3-like kinase BR-INSENSITIVE 2 (BIN2) acts as a key negative regulator in the BR signaling pathway, but the mechanisms regulating BIN2 function remain unclear. Here we report that the histone deacetylase HDA6 can interact with and deacetylate BIN2 to repress its kinase activity. The hda6 mutant showed a BR-repressed phenotype in the dark and was less sensitive to BR biosynt

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16

Liu, Jia, Xuan Wang, Yuanqin Zhu, et al. "Theabrownin from Dark Tea Ameliorates Insulin Resistance via Attenuating Oxidative Stress and Modulating IRS-1/PI3K/Akt Pathway in HepG2 Cells." Nutrients 15, no. 18 (2023): 3862. http://dx.doi.org/10.3390/nu15183862.

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Dark tea has great potential in regulating glycolipid metabolism, and theabrownin (TB) is considered to be the characteristic and bioactive constituent of dark tea. This study evaluated the ability of TB1 (fermented for 7 days) and TB2 (fermented for 14 days) isolated from dark tea to reverse insulin resistance (IR) in HepG2 cells. The results indicated that TB significantly ameliorated oxidative stress by improving mitochondrial function. In addition, TB improved glycogen synthesis and glucose consumption, and inhibited gluconeogenesis and fatty acid synthesis, by regulating GSK3β (Glycogen s

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17

Wykosky, Jill, Akitake Mukasa, Frank Furnari, and Webster K. Cavenee. "Escape from targeted inhibition: The dark side of kinase inhibitor therapy." Cell Cycle 9, no. 9 (2010): 1661–62. http://dx.doi.org/10.4161/cc.9.9.11592.

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18

Chu, Brian, Che-Hsiung Liu, Sukanya Sengupta, Amit Gupta, Padinjat Raghu, and Roger C. Hardie. "Common mechanisms regulating dark noise and quantum bump amplification in Drosophila photoreceptors." Journal of Neurophysiology 109, no. 8 (2013): 2044–55. http://dx.doi.org/10.1152/jn.00001.2013.

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Absolute visual thresholds are limited by “dark noise,” which in Drosophila photoreceptors is dominated by brief (∼10 ms), small (∼2 pA) inward current events, occurring at ∼2/s, believed to reflect spontaneous G protein activations. These dark events were increased in rate and amplitude by a point mutation in myosin III (NINAC), which disrupts its interaction with the scaffolding protein, INAD. This phenotype mimics that previously described in null mutants of ninaC (no inactivation no afterpotential; encoding myosin III) and an associated protein, retinophilin ( rtp). Dark noise was similarl

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19

Węgrzyn, Anna, Małgorzata Krysiak, Anna Kulik, Katarzyna B. Gieczewska, and Radosław Mazur. "STN7 Kinase Is Essential for Arabidopsis thaliana Fitness under Prolonged Darkness but Not under Dark-Chilling Conditions." International Journal of Molecular Sciences 23, no. 9 (2022): 4531. http://dx.doi.org/10.3390/ijms23094531.

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Reversible phosphorylation of photosystem II light harvesting complexes (LHCII) is a well-established protective mechanism enabling efficient response to changing light conditions. However, changes in LHCII phosphorylation were also observed in response to abiotic stress regardless of photoperiod. This study aimed to investigate the impact of dark-chilling on LHCII phosphorylation pattern in chilling-tolerant Arabidopsis thaliana and to check whether the disturbed LHCII phosphorylation process will impact the response of Arabidopsis to the dark-chilling conditions. We analyzed the pattern of L

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20

SENIN, Ivan I., Kevin R. DEAN, Aminullah A. ZARGAROV, Muhammad AKHTAR, and Pavel P. PHILIPPOV. "Recoverin inhibits the phosphorylation of dark-adapted rhodopsin more than it does that of bleached rhodopsin: a possible mechanism through which rhodopsin kinase is prevented from participation in a side reaction." Biochemical Journal 321, no. 2 (1997): 551–56. http://dx.doi.org/10.1042/bj3210551.

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In its resting state rhodopsin kinase is present in an inactive form and is activated after interaction with light-activated rhodopsin (Rho*). The activated rhodopsin kinase then phosphorylates Rho* but is also able to catalyse the phosphorylation of dark-adapted rhodopsin. A consequence of the latter behaviour of the activated kinase is that at low levels of bleach a large number of phosphoryl groups are incorporated per mol of Rho*. Recoverin- and Ca2+-dependent inhibition of rhodopsin kinase was found to be inversely related to the extent of bleaching; the lower the fraction of rhodopsin bl

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21

DEAN, Kevin R., and Muhammad AKHTAR. "Phosphorylatio of solubilised dark-adapted rhodopsin. Insights into the activation of rhodopsin kinase." European Journal of Biochemistry 213, no. 2 (1993): 881–90. http://dx.doi.org/10.1111/j.1432-1033.1993.tb17832.x.

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22

Tatar, Andra-Sorina, Timea Nagy-Simon, Adrian Bogdan Tigu, Ciprian Tomuleasa, and Sanda Boca. "Optimization of Tyrosine Kinase Inhibitor-Loaded Gold Nanoparticles for Stimuli-Triggered Antileukemic Drug Release." Journal of Functional Biomaterials 14, no. 8 (2023): 399. http://dx.doi.org/10.3390/jfb14080399.

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Tyrosine kinase inhibitor (TKI) therapy is gaining attraction in advanced cancer therapeutics due to the ubiquity of kinases in cell survival and differentiation. Great progress was made in the past years in identifying tyrosine kinases that can function as valuable molecular targets and for the entrapment of their corresponding inhibitors in delivery compounds for triggered release. Herein we present a class of drug-delivery nanocompounds based on TKI Midostaurin-loaded gold nanoparticles that have the potential to be used as theranostic agents for the targeting of the FMS-like tyrosine kinas

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23

Liu, Chang, Yichi Zhang, Yuqing Zhang, Zonghan Liu, Feifei Mao, and Zongtao Chai. "Mechanistic Insights into the Mechanism of Inhibitor Selectivity toward the Dark Kinase STK17B against Its High Homology STK17A." Molecules 27, no. 14 (2022): 4655. http://dx.doi.org/10.3390/molecules27144655.

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As a member of the death-associated protein kinase (DAPK) family, STK17B plays an important role in the regulation of cellular apoptosis and has been considered as a promising drug target for hepatocellular carcinoma. However, the highly conserved ATP-binding site of protein kinases represents a challenge to design selective inhibitors for a specific DAPK isoform. In this study, molecular docking, multiple large-scale molecular dynamics (MD) simulations, and binding free energy calculations were performed to decipher the molecular mechanism of the binding selectivity of PKIS43 toward STK17B ag

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24

Bronstein, Jeff, Claude G. Wasterlain, Robert Lasher, and Debora B. Farber. "Dark-induced changes in activity and compartmentalization of retinal calmodulin kinase in the rat." Brain Research 495, no. 1 (1989): 83–88. http://dx.doi.org/10.1016/0006-8993(89)91220-1.

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25

Žúbor, Vladimír, Albert Breier, Marta Horváthová, Dagmar Hagarová, Peter Gemeiner, and Danica Mislovičová. "Purification of Glycerol Kinase by "Dye-Ligand" Chromatography and Hydrophobic Interaction Chromatography on Bead-Cellulose Derivatives." Collection of Czechoslovak Chemical Communications 58, no. 2 (1993): 445–51. http://dx.doi.org/10.1135/cccc19930445.

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The crude extract of cytosole enzymes was obtained from homogenized cells of Saccharomyces cerevisiae by partition. The enzyme was then isolated from the lower aqueous phase displaying higher glycerol kinase activity by dye-ligand chromatography on Cibacron Blue (CB) or Remazol Brilliant Blue R (RB)-derivatized bead-cellulose, ATP being the eluent. The specific activity of glycerol kinase rised more than 10 and 7-times after affinity dye-ligand chromatography and hydrophobic interaction chromatography, respectively. Glycerol kinase obtained by the latter method was purified by CB-bead cellulos

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26

KOBAYASHI, Rumi, Yoshiharu SHIMOMURA, Taro MURAKAMI, et al. "Gender difference in regulation of branched-chain amino acid catabolism." Biochemical Journal 327, no. 2 (1997): 449–53. http://dx.doi.org/10.1042/bj3270449.

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Regulation of the activity state of the hepatic branched-chain 2-oxo acid dehydrogenase (BCODH) complex during the light-dark cycle differs markedly in male and female rats. Female rats exhibit a profound diurnal rhythm in the activity state of the complex that is not observed in male rats. Regardless of gender, most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats at the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive

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27

Priegnitz, Bert-Ewald, Ulrike Brandt, Khomaizon A. K. Pahirulzaman, Jeroen S. Dickschat, and André Fleißner. "The AngFus3 Mitogen-Activated Protein Kinase Controls Hyphal Differentiation and Secondary Metabolism in Aspergillus niger." Eukaryotic Cell 14, no. 6 (2015): 602–15. http://dx.doi.org/10.1128/ec.00018-15.

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ABSTRACTAdaptation to a changing environment is essential for the survival and propagation of sessile organisms, such as plants or fungi. Filamentous fungi commonly respond to a worsening of their growth conditions by differentiation of asexually or sexually produced spores. The formation of these specialized cell types is, however, also triggered as part of the general life cycle by hyphal age or density. Spores typically serve for dispersal and, therefore, translocation but can also act as resting states to endure times of scarcity. Eukaryotic differentiation in response to environmental and

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28

Sadiq, Nooruddin Bin, Hyukjoon Kwon, Nam Il Park, et al. "The Impact of Light Wavelength and Darkness on Metabolite Profiling of Korean Ginseng: Evaluating Its Anti-Cancer Potential against MCF-7 and BV-2 Cell Lines." International Journal of Molecular Sciences 24, no. 9 (2023): 7768. http://dx.doi.org/10.3390/ijms24097768.

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Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and

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29

Liepe, B. A., and B. Burnside. "Cyclic nucleotide regulation of teleost rod photoreceptor inner segment length." Journal of General Physiology 102, no. 1 (1993): 75–98. http://dx.doi.org/10.1085/jgp.102.1.75.

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Retinal rod photoreceptors of teleost fish elongate in the light and shorten in the dark. Rod cell elongation and shortening are both mediated by actin-dependent mechanisms that occur in the inner segment myoid and ellipsoid. The intracellular signaling pathways by which light and dark regulate the actin cytoskeleton in the inner segment are unknown. To investigate the intracellular signals that regulate teleost rod motility, we have been using mechanically isolated rod inner/outer segments (RIS-ROS) obtained from the retinas of green sunfish, Lepomis cyanellus. In culture, RIS-ROS retain the

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30

Frederiksen, Rikard, Soile Nymark, Alexander V. Kolesnikov, et al. "Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods." Journal of General Physiology 148, no. 1 (2016): 1–11. http://dx.doi.org/10.1085/jgp.201511538.

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Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore.

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31

Min, Jeong Uk, Duck Young Heo, and Sang Ho Kim. "The effect of the Intake Quantity of Dark Chocolate on the Aerobic Exercise Capacity, the Creatine Kinase Activity and Antioxidant Capacity." Journal of Sport and Leisure Studies 51 (February 28, 2013): 713–23. http://dx.doi.org/10.51979/kssls.2013.02.51.713.

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32

Donnelly, R. "Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research." British Journal of Ophthalmology 88, no. 1 (2004): 145–51. http://dx.doi.org/10.1136/bjo.88.1.145.

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33

Zuniga, Freddi Isaac, Gina H. Ochoa, Shannon D. Kelly, and Laura J. Robles. "S-crystallin and arginine kinase bind F-actin in light- and dark-adapted octopus retinas." Current Eye Research 28, no. 5 (2004): 343–50. http://dx.doi.org/10.1076/ceyr.28.5.343.28683.

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34

Lu, Jason, Tej Shidhaye, Peng Zhao, Lance Wells, Samiksha Katiyar, and Natarajan Kannan. "Abstract 1645 Characterization of the dark kinase DCLK3 reveals isoform-specific modification and novel substrates." Journal of Biological Chemistry 301, no. 5 (2025): 109913. https://doi.org/10.1016/j.jbc.2025.109913.

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35

ADAMS, Ryan A., Xinran LIU, David S. WILLIAMS, and Alexandra C. NEWTON. "Differential spatial and temporal phosphorylation of the visual receptor, rhodopsin, at two primary phosphorylation sites in mice exposed to light." Biochemical Journal 374, no. 2 (2003): 537–43. http://dx.doi.org/10.1042/bj20030408.

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Phosphorylation of rhodopsin critically controls the visual transduction cascade by uncoupling it from the G-protein transducin. The kinase primarily responsible for this phosphorylation is rhodopsin kinase, a substrate-regulated kinase that phosphorylates light-activated rhodopsin. Protein kinase C has been implicated in controlling the phosphorylation of both light-activated and dark-adapted rhodopsin. Two of the major rhodopsin phosphorylation sites in vivo, Ser334 and Ser338, are effective protein kinase C phosphorylation sites in vitro, while the latter is preferentially phosphorylated by

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36

Amrhein, Jennifer Alisa, Lena Marie Berger, Amelie Tjaden, et al. "Discovery of 3-Amino-1H-pyrazole-Based Kinase Inhibitors to Illuminate the Understudied PCTAIRE Family." International Journal of Molecular Sciences 23, no. 23 (2022): 14834. http://dx.doi.org/10.3390/ijms232314834.

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The PCTAIRE subfamily belongs to the CDK (cyclin-dependent kinase) family and represents an understudied class of kinases of the dark kinome. They exhibit a highly conserved binding pocket and are activated by cyclin Y binding. CDK16 is targeted to the plasma membrane after binding to N-myristoylated cyclin Y and is highly expressed in post-mitotic tissues, such as the brain and testis. Dysregulation is associated with several diseases, including breast, prostate, and cervical cancer. Here, we used the N-(1H-pyrazol-3-yl)pyrimidin-4-amine moiety from the promiscuous inhibitor 1 to target CDK16

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37

Nakasako, Masayoshi, Mao Oide, Yuki Takayama, Tomotaka Oroguchi, and Koji Okajima. "Domain Organization in Plant Blue-Light Receptor Phototropin2 of Arabidopsis thaliana Studied by Small-Angle X-ray Scattering." International Journal of Molecular Sciences 21, no. 18 (2020): 6638. http://dx.doi.org/10.3390/ijms21186638.

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Phototropin2 (phot2) is a blue-light (BL) receptor protein that regulates the BL-dependent activities of plants for efficient photosynthesis. Phot2 is composed of two light-oxygen-voltage sensing domains (LOV1 and LOV2) to absorb BL, and a kinase domain. Photo-activated LOV domains, especially LOV2, play a major role in photo-dependent increase in the phosphorylation activity of the kinase domain. The atomic details of the overall structure of phot2 and the intramolecular mechanism to convert BL energy to a phosphorylation signal remain unknown. We performed structural studies on the LOV fragm

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38

Stitt, Mark, Gottfried Mieskes, Hans-Dieter Söling, Heike Große, and Hans W. Heidt. "Diurnal Changes of Fructose-6-phosphate,2-kinase and Fructose-2,6-bis-phosphatase Activities in Spinach Leaves." Zeitschrift für Naturforschung C 41, no. 3 (1986): 291–96. http://dx.doi.org/10.1515/znc-1986-0308.

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Extracts have been rapidly prepared from spinach leaves, and the activity of fructose-6-phosphate, 2-kinase (Fru6P,2kinase) and fructose-2,6-bisphosphatase (Fru2.6P2ase) measured. The enzyme activities do not change during light-dark transitions, but there is an increase of Fru6P,2- kinase and decrease of Fru2,6P2ase activity over several hours in the light. This increase of the Fru6P,2kinase: Fru2,6P2:ase ratio shows that a previously unrecognized mechanism, which may include protein modification, controls Fru2,6P2 levels in leaves. It operates as sucrose accumulates in the leaf, and will be

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Drewry, David H., Carrow I. Wells, William J. Zuercher, and Timothy M. Willson. "A Perspective on Extreme Open Science: Companies Sharing Compounds without Restriction." SLAS DISCOVERY: Advancing the Science of Drug Discovery 24, no. 5 (2019): 505–14. http://dx.doi.org/10.1177/2472555219838210.

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Although the human genome provides the blueprint for life, most of the proteins it encodes remain poorly studied. This perspective describes how one group of scientists, in seeking new targets for drug discovery, used open science through unrestricted sharing of small molecules to shed light on dark matter of the genome. Starting initially with a single pharmaceutical company before expanding to multiple companies, a precedent was established for sharing published kinase inhibitors as chemical tools. The integration of open science and kinase chemogenomics has supported the study of many new p

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Tanaka, Susumu, Yoshiko Honda, Misa Sawachika, Kensuke Futani, Namika Yoshida, and Tohru Kodama. "Degradation of STK16 via KCTD17 with Ubiquitin–Proteasome System in Relation to Sleep–Wake Cycle." Kinases and Phosphatases 1, no. 1 (2022): 14–22. http://dx.doi.org/10.3390/kinasesphosphatases1010003.

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Serine/threonine-protein kinase 16 (STK16) is a novel member of the Numb-associated family of protein kinases with an atypical kinase domain. In this study, we aimed to investigate the involvement of STK16 in sleep–wake mechanisms. We confirmed the expression of Stk16 in the murine hypothalamus, the sleep–wake center, and found considerable changes in STK16 protein levels in the anterior hypothalamus during the light–dark cycle. We found that the coexistence of the potassium channel tetramerization domain containing 17 (KCTD17), an STK16 interactor, caused STK16 degradation. In contrast, the p

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Ling, Jun-Jie, Jian Li, Danmeng Zhu, and Xing Wang Deng. "Noncanonical role of Arabidopsis COP1/SPA complex in repressing BIN2-mediated PIF3 phosphorylation and degradation in darkness." Proceedings of the National Academy of Sciences 114, no. 13 (2017): 3539–44. http://dx.doi.org/10.1073/pnas.1700850114.

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The E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) has been known to mediate key signaling factors for degradation via the ubiquitin/26S proteasome pathway in both plants and animals. Here, we report a noncanonical function of Arabidopsis COP1, the central repressor of photomorphogenesis, in the form of a COP1/ SUPPRESSOR of phyA-105 (SPA) complex. We show that the COP1/SPA complex associates with and stabilizes PHYTOCHROME INTERACTING FACTOR 3 (PIF3) to repress photomorphogenesis in the dark. We identify the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) as a kinase of PIF3, which

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42

Marcus, Daniel C., Hiroshi Sunose, Jianzhong Liu, Zhijun Shen, and Margaret A. Scofield. "P2U purinergic receptor inhibits apical IsK/KvLQT1 channel via protein kinase C in vestibular dark cells." American Journal of Physiology-Cell Physiology 273, no. 6 (1997): C2022—C2029. http://dx.doi.org/10.1152/ajpcell.1997.273.6.c2022.

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Vestibular dark cells (VDC) are known to electrogenically secrete K+ via slowly activating K+(IsK) channels, consisting of IsK regulatory and KvLQT1 channel subunits, and the associated short-circuit current ( I sc) is inhibited by agonists of the apical P2U(P2Y2) receptor (J. Liu, K. Kozakura, and D. C. Marcus. Audit. Neurosci. 2: 331–340, 1995). Measurements of relative K+ flux ( J K) with a self-referencing K+-selective probe demonstrated a decrease in J K after apical perfusion of 100 μM ATP. On-cell macropatch recordings from gerbil VDC showed a decrease of the IsKchannel current ( I IsK)

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Amiteye, Samuel, Kazuo Kobayashi, Daisuke Imamura, Shigeo Hosoya, Naotake Ogasawara, and Tsutomu Sato. "Bacillus subtilis Diacylglycerol Kinase (DgkA) Enhances Efficient Sporulation." Journal of Bacteriology 185, no. 17 (2003): 5306–9. http://dx.doi.org/10.1128/jb.185.17.5306-5309.2003.

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ABSTRACT The sn-1,2-diacylglycerol kinase homologue gene, dgkA, is a sporulation gene indispensable for the maintenance of spore stability and viability in Bacillus subtilis. After 6 h of growth in resuspension medium, the endospore morphology of the dgkA mutant by standard phase-contrast microscopy was normal; however, after 9 h, the endospores appeared mostly dark by phase-contrast microscopy, suggesting a defect in the spores. Moreover, electron microscopic studies revealed an abnormal cortex structure in mutant endospores 6 h after the onset of sporulation, an indication of cortex degenera

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Dikiy, Igor, Uthama R. Edupuganti, Rinat R. Abzalimov, et al. "Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346." Proceedings of the National Academy of Sciences 116, no. 11 (2019): 4963–72. http://dx.doi.org/10.1073/pnas.1813586116.

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Translation of environmental cues into cellular behavior is a necessary process in all forms of life. In bacteria, this process frequently involves two-component systems in which a sensor histidine kinase (HK) autophosphorylates in response to a stimulus before subsequently transferring the phosphoryl group to a response regulator that controls downstream effectors. Many details of the molecular mechanisms of HK activation are still unclear due to complications associated with the multiple signaling states of these large, multidomain proteins. To address these challenges, we combined complemen

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ROY, DEBORAH R. SAMANTA, and COLIN J. BARNSTABLE. "Developmental expression of intracellular targets of cGMP in rat visual cortex and alteration with dark rearing." Visual Neuroscience 18, no. 1 (2001): 109–18. http://dx.doi.org/10.1017/s0952523801181101.

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We describe the temporal pattern of mRNA expression of some of the molecular components of the NO/cGMP second messenger system in the developing rat visual cortex and the effect of dark rearing on their expression levels using semiquantitative RT-PCR. mRNA expression for these molecules was altered by dark rearing in one of three ways: (1) no change—rod, olfactory, and cone/testis CNG channels, nonselective cation channels gated by cyclic nucleotides and highly permeable to Ca2+; (2) decrease—cyclic nucleotide phosphodiesterases which regulate cyclic nucleotide levels, and soluble guanylyl cyc

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46

Kowallik, Wolfgang, Meinolf Thiemann, Yi Huang, et al. "Complete Sequence of Glycolytic Enzymes in the Mycorrhizal Basidiomycete, Suillus bovinus." Zeitschrift für Naturforschung C 53, no. 9-10 (1998): 818–27. http://dx.doi.org/10.1515/znc-1998-9-1007.

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Axenic cultures of Suillus bovinus were cultivated in inorganic liquid medium with glucose as a carbon source at 25 °C and continuous supply of oxygen by aeration with compressed air in the dark. Exogenous fructose as sole carbon source yielded about 50% less increase in dry weight than glucose. This resulted from different uptake velocities. Sucrose as sole exogenous carbon source yielded no measurable increase in dry weight. In glucose cultures, activities of all glycolytic enzymes were found. Maximum specific activities varied largely (from about 60 [fructose 6-phosphate kinase] to about 20

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Kolesnikov, Alexander V., Tivadar Orban, Hui Jin, et al. "Dephosphorylation by protein phosphatase 2A regulates visual pigment regeneration and the dark adaptation of mammalian photoreceptors." Proceedings of the National Academy of Sciences 114, no. 45 (2017): E9675—E9684. http://dx.doi.org/10.1073/pnas.1712405114.

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Resetting of G-protein–coupled receptors (GPCRs) from their active state back to their biologically inert ground state is an integral part of GPCR signaling. This “on–off” GPCR cycle is regulated by reversible phosphorylation. Retinal rod and cone photoreceptors arguably represent the best-understood example of such GPCR signaling. Their visual pigments (opsins) are activated by light, transduce the signal, and are then inactivated by a GPCR kinase and arrestin. Although pigment inactivation by phosphorylation is well understood, the enzyme(s) responsible for pigment dephosphorylation and the

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Long, Brit, Elisha Targonsky, and Alex Koyfman. "Just the Facts: Diagnosis and management of rhabdomyolysis." CJEM 22, no. 6 (2020): 745–48. http://dx.doi.org/10.1017/cem.2020.37.

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A 32-year-old male presents with diffuse myalgias, weakness, and dark urine for 1 day. The patient states he recently started a new exercise program. He is hemodynamically stable, and his physical examination reveals diffuse muscle tenderness. His creatine kinase (CK) returns at 8,000 international units per liter (IU/L), and his urinalysis reveals blood but only three red blood cells (RBCs) on microscopy.

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Spicer, S. S., and B. A. Schulte. "Creatine kinase in epithelium of the inner ear." Journal of Histochemistry & Cytochemistry 40, no. 2 (1992): 185–92. http://dx.doi.org/10.1177/40.2.1313059.

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Epithelium of the inner ear in the gerbil and mouse was examined immunocytochemically for presence of creatine kinase (CK). Marginal cells of the cochlear stria vascularis and dark cells and transitional cells of the vestibular system were found to contain an abundance of the MM isozyme (MM-CK). CK in these cells concurs with that which is coupled to Na,K-ATPase in other cells and is considered to supply ATP for the Na,K-ATPase that mediates the high KCl of endolymph. Inner hair cells revealed content of the BB isozyme and in this respect resembled the energy-transducing photoreceptor cells in

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Catelli, Arianna, Cristina Nanni, Rita Mulè та ін. "The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET". Journal of Clinical Medicine 13, № 8 (2024): 2203. http://dx.doi.org/10.3390/jcm13082203.

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Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin’s lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone

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