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https://www.readbyqxmd.com/read/28634229/akt-activation-by-ca2-calmodulin-dependent-protein-kinase-kinase-2-camkk2-in-ovarian-cancer-cells
#1
Angela M Gocher, Gissou Azabdaftari, Lindsey M Euscher, Shuhang Dai, Loukia G Karacosta, Thomas F Franke, Arthur M Edelman
Hyperactivation of Akt is associated with oncogenic changes in the growth, survival and chemoresistance of cancer cells. The PI3K/Phosphoinositide-dependent kinase (PDK) 1 pathway represents the canonical mechanism for phosphorylation of Akt at its primary activation site, Thr308. We observed that Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (beta) (CaMKK2) is highly expressed in high-grade serous ovarian cancer and investigated its role in Akt activation in ovarian cancer (OVCa) cell lines (OVCAR-3, SKOV-3, Caov-3)...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28633902/calcium-sensing-receptor-initiating-cystathionine-gamma-lyase-hydrogen-sulfide-pathway-to-inhibit-platelet-activation-in-hyperhomocysteinemia-rat
#2
Yuwen Wang, Ziqing Zhao, Sa Shi, Fei Gao, Jichao Wu, Shiyun Dong, Weihua Zhang, Yanhong Liu, Xin Zhong
Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H2S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H2S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)/H2S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured...
June 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28626614/identification-of-two-cigads-from-caragana-intermedia-and-their-transcriptional-responses-to-abiotic-stresses-and-exogenous-abscisic-acid
#3
Jing Ji, Lingyu Zheng, Jianyun Yue, Xiamei Yao, Ermei Chang, Tiantian Xie, Nan Deng, Lanzhen Chen, Yuwen Huang, Zeping Jiang, Shengqing Shi
BACKGROUND: Glutamate decarboxylase (GAD), as a key enzyme in the γ -aminobutyric acid (GABA) shunt, catalyzes the decarboxylation of L-glutamate to form GABA. This pathway has attracted much interest because of its roles in carbon and nitrogen metabolism, stress responses, and signaling in higher plants. The aim of this study was to isolate and characterize genes encoding GADs from Caragana intermedia, an important nitrogen-fixing leguminous shrub. METHODS: Two full-length cDNAs encoding GADs (designated as CiGAD1 and CiGAD2) were isolated and characterized...
2017: PeerJ
https://www.readbyqxmd.com/read/28623230/flexible-body-motions-of-calmodulin-and-the-farnesylated-hypervariable-region-yield-a-high-affinity-interaction-enabling-k-ras4b-membrane-extraction
#4
Hyunbum Jang, Avik Banerjee, Tanmay Chavan, Vadim Gaponenko, Ruth Nussinov
In calmodulin (CaM)-rich environments, oncogenic KRAS plays a critical role in adenocarcinomas by promoting PI3K/Akt signaling. We previously proposed that at elevated calcium levels in cancer, CaM recruits PI3Kα to the membrane and extracts K-Ras4B from the membrane, organizing a K-Ras4B/CaM/PI3Kα ternary complex. CaM can thereby replace a missing receptor tyrosine kinase signal to fully activate PI3Kα. Recent experimental data show that CaM selectively promotes K-Ras signaling, but not of N-Ras or H-Ras...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28620084/multidimensional-genetic-analysis-of-repeated-seizures-in-the-hybrid-mouse-diversity-panel-reveals-a-novel-epileptogenesis-susceptibility-locus
#5
Russell J Ferland, Jason Smith, Dominick Papandrea, Jessica Gracias, Leah Hains, Sridhar B Kadiyala, Brittany O'Brien, Eun Yong Kang, Barbara S Beyer, Bruce J Herron
Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology...
June 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28615325/calcium-calmodulin-dependent-protein-kinase-regulates-the-pink1-parkin-and-dj-1-pathways-of-mitophagy-during-sepsis
#6
Xianghong Zhang, Du Yuan, Qian Sun, Li Xu, Emma Lee, Anthony J Lewis, Brian S Zuckerbraun, Matthew R Rosengart
During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential (ΔΨ) and mitophagy has not been identified. Mitochondria also buffer Ca(2+), and their buffering capacity is dependent on ΔΨ...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28614711/dapk1-mediates-ltd-by-making-camkii-glun2b-binding-ltp-specific
#7
Dayton J Goodell, Vincent Zaegel, Steven J Coultrap, Johannes W Hell, K Ulrich Bayer
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28614631/trpm4-regulates-akt-gsk3-%C3%AE-activity-and-enhances-%C3%AE-catenin-signaling-and-cell-proliferation-in-prostate-cancer-cells
#8
Alfredo I Sagredo, Eduardo A Sagredo, Claudio Cappelli, Pablo Báez, Andaur M Rodrigo, Constanza Blanco, Julio C Tapia, César Echeverría, Oscar Cerda, Andrés Stutzin, Felipe Simon, Katherine Marcelain, Ricardo Armisén
Increased expression of the TRPM4 channel has been reported to be associated with the progression of prostate cancer. However, the molecular mechanism underlying its effect remains unknown. This work found that decreasing TRPM4 levels leads to the reduced proliferation of PC3 cells. This effect was associated with a decrease in total β-catenin protein levels and its nuclear localization, and a significant reduction in Tcf/Lef transcriptional activity. Moreover, TRPM4 silencing increases the Ser33/Ser37/Thr41 β-catenin phosphorylated population and reduces the phosphorylation of GSK-3β at Ser9, suggesting an increase in β-catenin degradation as the underlying mechanism...
June 14, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28612156/reduction-of-sr-ca-2-leak-and-arrhythmogenic-cellular-correlates-by-smp-114-a-novel-camkii-inhibitor-with-oral-bioavailability
#9
Stefan Neef, Christian Mann, Anne Zwenger, Nataliya Dybkova, Lars S Maier
Sarcoplasmic reticulum (SR) Ca(2+) leak induced by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is centrally involved in atrial and ventricular arrhythmogenesis as well as heart failure remodeling. Consequently, treating SR Ca(2+) leak has been proposed as a novel therapeutic paradigm, but compounds for use in humans are lacking. SMP-114 ("Rimacalib") is a novel, orally available CaMKII inhibitor developed for human use that has already entered clinical phase II trials to treat rheumatoid arthritis...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28611207/adult-ventricular-myocytes-segregate-kcnq1-and-kcne1-to-keep-the-iks-amplitude-in-check-until-when-larger-iks-is-needed
#10
Min Jiang, Yuhong Wang, Gea-Ny Tseng
BACKGROUND: KCNQ1 and KCNE1 assemble to form the slow delayed rectifier (IKs) channel critical for shortening ventricular action potentials during high β-adrenergic tone. However, too much IKs under basal conditions poses an arrhythmogenic risk. Our objective is to understand how adult ventricular myocytes regulate the IKs amplitudes under basal conditions and in response to stress. METHODS AND RESULTS: We express fluorescently tagged KCNQ1 and KCNE1 in adult ventricular myocytes and follow their biogenesis and trafficking paths...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28608248/the-analgesic-effect-of-trans-resveratrol-is-regulated-by-calcium-channels-in-the-hippocampus-of-mice
#11
Weijie Wang, Yingcong Yu, Jing Li, Lin Wang, Zhi Li, Chong Zhang, Linlin Zhen, Lianshu Ding, Gang Wang, Xiaoyang Sun, Ying Xu
Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca(2+)/calmodulin-dependent signaling in the spinal cord of mice...
June 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28604807/brain-derived-neurotrophic-factor-bdnf-trkb-signaling-modulates-cancer-endothelial-cells-interaction-and-affects-the-outcomes-of-triple-negative-breast-cancer
#12
Yi-Fang Tsai, Ling-Ming Tseng, Chih-Yi Hsu, Muh-Hwa Yang, Jen-Hwey Chiu, Yi-Ming Shyr
AIMS: There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. METHODS: We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC...
2017: PloS One
https://www.readbyqxmd.com/read/28603528/cml20-an-arabidopsis-calmodulin-like-protein-negatively-regulates-guard-cell-aba-signaling-and-drought-stress-tolerance
#13
Xiaomeng Wu, Zhu Qiao, Huiping Liu, Biswa R Acharya, Chunlong Li, Wei Zhang
Guard cells shrink in response to drought and abscisic acid (ABA), which is caused by efflux of ions that in turn reduces stomatal aperture and improves the plant's ability to retain moisture. Cytosolic free calcium is an essential secondary messenger in guard cell ABA signaling, but the details of this regulatory pathway remain sketchy. Here, the calmodulin-like protein CML20, which has four EF-hand domains and calcium-binding activity in vitro, was found to be a negative regulator of ABA-induced stomatal movement in Arabidopsis...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28602681/characterization-and-function-of-a-novel-calmodulin-like-protein-from-crayfish-procambarus-clarkii
#14
Baojian Zhu, Yingying Yu, Jin Gao, Yuanyuan Feng, Lin Tang, Yuxuan Sun, Liangli Yang
Calmodulin plays an important role in calcium-dependent signal transduction pathways. In this experiment, a novel calmodulin-like gene (Pc-CaM-L) was identified in the crayfish Procambarus clarkia; it encodes a polypeptide of 145 amino acids. Quantitative real-time PCR analysis revealed that Pc-CaM-L was expressed in all examined tissues, including hepatopancreas, hemocytes, heart, gill, intestine and muscle; the highest Pc-CaM-L expression level was detected in the hepatopancreas. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot analysis demonstrated that a recombinant Pc-CaM-L protein was successfully expressed in Escherichia coli...
June 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28600177/compound-heterozygous-kcnq1-mutations-a300t-p535t-in-a-child-with-sudden-unexplained-death-insights-into-possible-molecular-mechanisms-based-on-protein-modeling
#15
Erika Antúnez-Argüelles, Arturo Rojo-Domínguez, Ana Leticia Arregui-Mena, Leonor Jacobo-Albavera, Manlio Fabio Márquez, Pedro Iturralde-Torres, María Teresa Villarreal-Molina
Sudden death in a child is a devastating event with important medical implications for surviving relatives. Because it may be the first manifestation of unknown inherited cardiac disease, molecular autopsy can be helpful to determine the cause of death and identify at risk family members. The aim of the study was to perform a molecular autopsy in a seven year-old girl with sudden unexplained death, to find evidence supporting the possible pathogenicity of mutations identified in inherited cardiac disease genes, and to clinically and genetically assess first-degree relatives...
June 6, 2017: Gene
https://www.readbyqxmd.com/read/28598584/camels-in-silico-prediction-of-calmodulin-binding-proteins-and-their-binding-sites
#16
Wajid Arshad Abbasi, Amina Asif, Saiqa Andleeb, Fayyaz Ul Amir Afsar Minhas
Due to Ca(2+) -dependent binding and the sequence diversity of Calmodulin (CaM) binding proteins, identifying CaM interactions and binding sites in the wet-lab is tedious and costly. Therefore, computational methods for this purpose are crucial to the design of such wet-lab experiments. We present an algorithm suite called CaMELS (CalModulin intEraction Learning System) for predicting proteins that interact with CaM as well as their binding sites using sequence information alone. CaMELS offers state of the art accuracy for both CaM interaction and binding site prediction and can aid biologists in studying CaM binding proteins...
June 9, 2017: Proteins
https://www.readbyqxmd.com/read/28597397/protein-kinase-c%C3%AE-gene-depletion-protects-against-methamphetamine-induced-impairments-in-recognition-memory-and-erk1-2-signaling-via-upregulation-of-glutathione-peroxidase-1-gene
#17
The-Vinh Tran, Eun-Joo Shin, Lan Thuy Ty Nguyen, Youngho Lee, Dae-Joong Kim, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kazuya Toriumi, Toshitaka Nabeshima, Kiyofumi Yamada, Hyoung-Chun Kim
Accumulating evidence has suggested that repeated treatment with methamphetamine (MA) resulted in cognitive impairments. Importantly, we show that selective upregulation of protein kinase Cδ (PKCδ) in the prefrontal cortex (PFC) of wild-type mice persisted for 28 days post withdrawal of MA. On day 28, the MA-induced increase in phospho-PKCδ expression and decrease in phospho-ERK1/2 expression were significantly attenuated by both the Src inhibitor PP2 and the dopamine D1 receptor antagonist SCH 23390. However, neither protein kinase A inhibitor H89 nor calmodulin-dependent protein kinase II inhibitor KN93 attenuated MA-induced alterations in phospho-PKCδ expression and phospho-ERK1/2 expression...
June 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28597297/intrinsic-protein-disorder-in-oncogenic-kras-signaling
#18
REVIEW
Ruth Nussinov, Hyunbum Jang, Chung-Jung Tsai, Tsung-Jen Liao, Shuai Li, David Fushman, Jian Zhang
How Ras, and in particular its most abundant oncogenic isoform K-Ras4B, is activated and signals in proliferating cells, poses some of the most challenging questions in cancer cell biology. In this paper, we ask how intrinsically disordered regions in K-Ras4B and its effectors help promote proliferative signaling. Conformational disorder allows spanning long distances, supports hinge motions, promotes anchoring in membranes, permits segments to fulfil multiple roles, and broadly is crucial for activation mechanisms and intensified oncogenic signaling...
June 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28596783/analysis-of-ef-hand-proteins-in-soybean-genome-suggests-their-potential-roles-in-environmental-and-nutritional-stress-signaling
#19
Houqing Zeng, Yaxian Zhang, Xiajun Zhang, Erxu Pi, Yiyong Zhu
Calcium ion (Ca(2+)) is a universal second messenger that plays a critical role in plant responses to diverse physiological and environmental stimuli. The stimulus-specific signals are perceived and decoded by a series of Ca(2+) binding proteins serving as Ca(2+) sensors. The majority of Ca(2+) sensors possess the EF-hand motif, a helix-loop-helix structure which forms a turn-loop structure. Although EF-hand proteins in model plant such as Arabidopsis have been well described, the identification, classification, and the physiological functions of EF-hand-containing proteins from soybean are not systemically reported...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28596776/genome-wide-association-mapping-of-loci-associated-with-plant-growth-and-forage-production-under-salt-stress-in-alfalfa-medicago-sativa-l
#20
Xiang-Ping Liu, Long-Xi Yu
Salinity tolerance is highly desirable to sustain alfalfa production in marginal lands that have been rendered saline. In this study, we used a diverse panel of 198 alfalfa accessions for mapping loci associated with plant growth and forage production under salt stress using genome-wide association studies (GWAS). The plants were genotyped using genotyping-by-sequencing (GBS). A greenhouse procedure was used for phenotyping four agronomic and physiological traits affected by salt stress, including dry weight (DW), plant height (PH), leaf chlorophyll content (LCC), and stomatal conductance (SC)...
2017: Frontiers in Plant Science
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