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phosphoproteomics

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https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#1
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28079298/from-phosphoproteins-to-phosphoproteomes-a-historical-account
#2
REVIEW
Andrea Venerando, Luca Cesaro, Lorenzo A Pinna
The first phosphoprotein (casein) was discovered in 1883, yet the enzyme responsible for its phosphorylation was identified only 130 years later, in 2012. During the very long time elapsed between these two events, with special reference to the last decades of the 1900s, it became evident that, far from being an oddity, phosphorylation affects the majority of eukaryotic proteins during their lifespan, and that this reaction is catalysed by the members of a large family of protein kinases, susceptible to a variety of stimuli controlling nearly every aspects of life and death...
January 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28076760/enriching-the-circadian-proteome
#3
Joseph S Takahashi
Circadian clocks regulate most aspects of physiology and metabolism. Genome-wide approaches have uncovered widespread circadian rhythms in the transcriptome, cistrome, and epigenome of mice, and now two proteomics studies in this issue (Robles et al., 2016; Wang et al., 2016) reveal extensive circadian regulation of the nuclear and phosphoproteome.
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28073184/functional-lipidomics-palmitic-acid-impairs-hepatocellular-carcinoma-development-by-modulating-membrane-fluidity-and-glucose-metabolism
#4
Ling Lin, Ying Ding, Yi Wang, Zhenxin Wang, Xuefei Yin, Guoquan Yan, Lei Zhang, Pengyuan Yang, Huali Shen
: Lipids are essential cellular components and energy sources of living organisms, altered lipid composition is increasingly recognized as a signature of cancer. We performed the lipidomic analysis in a series of hepatocellular carcinoma (HCC) cells and identified over 1700 intact lipids originating from 3 major lipid categories. Comparative lipidomic screening revealed 93 significantly changed lipids and decreased palmitic acyl (C16:0)-containing glycerophospholipids (GPs) were positively associated with metastatic abilities of HCC cells...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28072816/systematic-analysis-of-transcriptional-and-post-transcriptional-regulation-of-metabolism-in-yeast
#5
Emanuel Gonçalves, Zrinka Raguz Nakic, Mattia Zampieri, Omar Wagih, David Ochoa, Uwe Sauer, Pedro Beltrao, Julio Saez-Rodriguez
Cells react to extracellular perturbations with complex and intertwined responses. Systematic identification of the regulatory mechanisms that control these responses is still a challenge and requires tailored analyses integrating different types of molecular data. Here we acquired time-resolved metabolomics measurements in yeast under salt and pheromone stimulation and developed a machine learning approach to explore regulatory associations between metabolism and signal transduction. Existing phosphoproteomics measurements under the same conditions and kinase-substrate regulatory interactions were used to in silico estimate the enzymatic activity of signalling kinases...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28064214/hsp90-promotes-burkitt-lymphoma-cell-survival-by-maintaining-tonic-b-cell-receptor-signaling
#6
Roland Walter, Kuan-Ting Pan, Carmen Doebele, Federico Comoglio, Katarzyna Tomska, Hanibal Bohnenberger, Ryan M Young, Laura Jacobs, Ulrich Keller, Halvard Bönig, Michael Engelke, Andreas Rosenwald, Henning Urlaub, Louis M Staudt, Hubert Serve, Thorsten Zenz, Thomas Oellerich
Burkitt lymphoma (BL) is an aggressive B cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Due to their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28062706/combinatorial-drug-screening-identifies-ewing-sarcoma-specific-sensitivities
#7
Branka Radic-Sarikas, Kalliopi P Tsafou, Kristina B Emdal, Theodore Papamarkou, Kilian V M Huber, Cornelia Mutz, Jeffrey A Toretsky, Keiryn L Bennett, Jesper V Olsen, Søren Brunak, Heinrich Kovar, Giulio Superti-Furga
Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28060719/temporal-quantitative-phosphoproteomics-of-adp-stimulation-reveals-novel-central-nodes-in-platelet-activation-and-inhibition
#8
Florian Beck, Jörg Geiger, Stepan Gambaryan, Fiorella A Solari, Margherita Dell'Aica, Stefan Loroch, Nadine Mattheij, Igor Mindukshev, Oliver Pötz, Kerstin Jurk, Julia M Burkhart, Christian Fufezan, Johan W M Heemskerk, Ulrich Walter, René P Zahedi, Albert Sickmann
ADP enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades leading to integrin αIIbβ3 activation, a process that is antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful anti-platelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (i) critical hubs in platelet signaling towards aggregation, and (ii) novel molecular targets for anti-platelet treatment strategies...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28059163/phosphoproteomic-comparison-of-pik3ca-and-pten-signalling-identifies-the-nucleotidase-nt5c-as-a-novel-akt-substrate
#9
Larissa S Moniz, Silvia Surinova, Essam Ghazaly, Lorena Gonzalez Velasco, Syed Haider, Juan Carlos Rodríguez-Prados, Inma M Berenjeno, Claude Chelala, Bart Vanhaesebroeck
To identify novel effectors and processes regulated by PI3K pathway activation, we performed an unbiased phosphoproteomic screen comparing two common events of PI3K deregulation in cancer: oncogenic Pik3ca mutation (Pik3ca(H1047R)) and deletion of Pten. Using mouse embryonic fibroblast (MEF) models that generate inducible, low-level pathway activation as observed in cancer, we quantified 7566 unique phosphopeptides from 3279 proteins. A number of proteins were found to be differentially-regulated by Pik3ca(H1047R) and Pten loss, suggesting unique roles for these two events in processes such as vesicular trafficking, DNA damage repair and RNA splicing...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054942/a-comprehensive-proteomic-survey-of-aba-induced-protein-phosphorylation-in-rice-oryza-sativa-l
#10
Jiehua Qiu, Yuxuan Hou, Yifeng Wang, Zhiyong Li, Juan Zhao, Xiaohong Tong, Haiyan Lin, Xiangjin Wei, Hejun Ao, Jian Zhang
abscisic acid (ABA) is a key phytohormone regulating plant development and stress response. The signal transduction of ABA largely relies on protein phosphorylation. However; little is known about the phosphorylation events occurring during ABA signaling in rice thus far. By employing a label-free; MS (Mass Spectrometry)-based phosphoproteomic approach; we identified 2271 phosphosites of young rice seedlings and their intensity dynamics in response to ABA; during which 1060 proteins were found to be differentially phosphorylated...
January 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28039027/the-map-kinase-mapklk1-is-essential-to-trypanosoma-brucei-and-has-potential-targets-related-to-mrna-metabolism
#11
Michel Batista, Fernanda G Kugeratski, Carla Vp Lima, Christian M Probst, Rafael L Kessler, Lyris Mf de Godoy, Marco A Krieger, Fabricio K Marchini
: Protein phosphorylation and dephosphorylation events regulate many cellular processes. The identification of all phosphorylation sites and their association to a respective protein kinase or phosphatase is a challenging and crucial step to have a deeper understanding of the effects of signaling networks on cells. Pathogenic trypanosomatids have a large number of protein kinases and phosphatases in comparison to other organisms, which reinforces the relevance of the phosphorylation process in these early eukaryotes, nevertheless little is known about protein phosphorylation in these protozoa...
December 27, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/28028127/myofibrillar-z-discs-are-a-protein-phosphorylation-hot-spot-with-pkc-%C3%AE-modulating-protein-dynamics
#12
Lena Reimann, Heike Wiese, Yvonne Leber, Anja N Schwäble, Anna L Fricke, Anne Rohland, Bettina Knapp, Christian D Peikert, Friedel Drepper, Peter F M van der Ven, Gerald Radziwill, Dieter O Fürst, Bettina Warscheid
The Z-disc is a protein-rich structure critically important for the development and integrity of myofibrils, which are the contractile organelles of cross-striated muscle cells. We here used mouse C2C12 myoblast which were differentiated into myotubes followed by electrical pulse stimulation (EPS) to generate contracting myotubes comprising mature Z-discs. Using a quantitative proteomics approach, we analyzed changes in the relative abundance of 2,588 proteins, of which 387 were significantly regulated in myoblasts versus myotubes...
December 27, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28011693/protein-phosphatase-2cs-and-microtubule-associated-stress-protein-1-control-microtubule-stability-plant-growth-and-drought-response
#13
Govinal Badiger Bhaskara, Tuan-Nan Wen, Thao Thi Nguyen, Paul E Verslues
Plant growth is coordinated with environmental factors, including water availability during times of drought. Microtubules influence cell expansion; however, the mechanisms by which environmental signals impinge upon microtubule organization and whether microtubule-related factors limit growth during drought remains unclear. We found that three Clade E Growth-Regulating (EGR) type 2 C protein phosphatases act as negative growth regulators to restrain growth during drought. Quantitative phosphoproteomics indicated that EGRs target cytoskeleton and plasma membrane-associated proteins...
December 23, 2016: Plant Cell
https://www.readbyqxmd.com/read/28009266/elucidation-of-signaling-pathways-from-large-scale-phosphoproteomic-data-using-protein-interaction-networks
#14
Jan Daniel Rudolph, Marjo de Graauw, Bob van de Water, Tamar Geiger, Roded Sharan
Phosphoproteomic experiments typically identify sites within a protein that are differentially phosphorylated between two or more cell states. However, the interpretation of these data is hampered by the lack of methods that can translate site-specific information into global maps of active proteins and signaling networks, especially as the phosphoproteome is often undersampled. Here, we describe PHOTON, a method for interpreting phosphorylation data within their signaling context, as captured by protein-protein interaction networks, to identify active proteins and pathways and pinpoint functional phosphosites...
December 21, 2016: Cell Systems
https://www.readbyqxmd.com/read/28008135/gfat1-phosphorylation-by-ampk-promotes-vegf-induced-angiogenesis
#15
Darya Zibrova, Franck Vandermoere, Olga Göransson, Mark Peggie, Karina Mariño, Anne Knierim, Katrin Spengler, Cora Weigert, Benoit Viollet, Nicholas A Morrice, Kei Sakamoto, Regine Heller
Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood. Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate. GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches...
December 22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/28004756/alteration-of-platelet-gpvi-signaling-in-st-elevation-myocardial-infarction-patients-demonstrated-by-a-combination-of-proteomic-biochemical-and-functional-approaches
#16
Paula Vélez, Raymundo Ocaranza-Sánchez, Diego López-Otero, Lilian Grigorian-Shamagian, Isaac Rosa, Esteban Guitián, José María García-Acuña, José Ramón González-Juanatey, Ángel García
The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide)...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27998275/efficient-randomization-of-biological-networks-while-preserving-functional-characterization-of-individual-nodes
#17
Francesco Iorio, Marti Bernardo-Faura, Andrea Gobbi, Thomas Cokelaer, Giuseppe Jurman, Julio Saez-Rodriguez
BACKGROUND: Networks are popular and powerful tools to describe and model biological processes. Many computational methods have been developed to infer biological networks from literature, high-throughput experiments, and combinations of both. Additionally, a wide range of tools has been developed to map experimental data onto reference biological networks, in order to extract meaningful modules. Many of these methods assess results' significance against null distributions of randomized networks...
December 20, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27987026/phosphoproteomics-of-colon-cancer-metastasis-comparative-mass-spectrometric-analysis-of-the-isogenic-primary-and-metastatic-cell-lines-sw480-and-sw620
#18
Alissa J Schunter, Xiaoshan Yue, Amanda B Hummon
The contributions of phosphorylation-mediated signaling networks to colon cancer metastasis are poorly defined. To interrogate constitutive signaling alterations in cancer progression, the global phosphoproteomes of patient-matched SW480 (primary colon tumor origin) and SW620 (lymph node metastasis) cell lines were compared with TiO2 and immobilized metal affinity chromatography phosphopeptide enrichment followed by liquid chromatography-tandem mass spectrometry. Network analysis of the significantly altered phosphosites revealed differential regulation in cellular adhesion, mitosis, and messenger RNA translational machinery...
December 16, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27986865/crosstalks-via-mtorc2-can-explain-enhanced-activation-in-response-to-insulin-in-diabetic-patients
#19
Rasmus Magnusson, Mika Gustafsson, Gunnar Cedersund, Peter Strålfors, Elin Nyman
The molecular mechanisms of insulin resistance in type 2 diabetes have been extensively studied in primary human adipocytes, and mathematical modelling has clarified the central role of attenuation of mTORC1 activity in the diabetic state. Attenuation of mTORC1 in diabetes quells insulin signalling network-wide, except for the mTORC2-catalysed phosphorylation of PKB at serine-473, which is increased. This unique increase could potentially be explained by feedback and inter-branch crosstalk signals. To examine if such mechanisms operate in adipocytes, we herein analysed data from an un-biased phosphoproteomic screen in 3T3-L1 adipocytes...
December 16, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27984725/cdk-substrate-phosphorylation-and-ordering-the-cell-cycle
#20
Matthew P Swaffer, Andrew W Jones, Helen R Flynn, Ambrosius P Snijders, Paul Nurse
S phase and mitotic onset are brought about by the action of multiple different cyclin-CDK complexes. However, it has been suggested that changes in the total level of CDK kinase activity, rather than substrate specificity, drive the temporal ordering of S phase and mitosis. Here, we present a phosphoproteomics-based systems analysis of CDK substrates in fission yeast and demonstrate that the phosphorylation of different CDK substrates can be temporally ordered during the cell cycle by a single cyclin-CDK. This is achieved by rising CDK activity and the differential sensitivity of substrates to CDK activity over a wide dynamic range...
December 15, 2016: Cell
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