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phosphoproteomics

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https://www.readbyqxmd.com/read/29234155/analysis-of-neuronal-phosphoproteome-reveals-pink1-regulation-of-bad-function-and-cell-death
#1
Huida Wan, Bin Tang, Xun Liao, Qiufang Zeng, Zhuohua Zhang, Lujian Liao
PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress...
December 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29233185/phosphoproteomics-reveals-network-rewiring-to-a-pro-adhesion-state-in-annexin-1-deficient-mammary-epithelial-cells
#2
Asfa Alli-Shaik, Sheena Wee, Lina H K Lim, Jayantha Gunaratne
BACKGROUND: Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells...
December 12, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29229832/fkbp12-contributes-to-%C3%AE-synuclein-toxicity-by-regulating-the-calcineurin-dependent-phosphoproteome
#3
Gabriela Caraveo, Martin Soste, Valentina Cappelleti, Saranna Fanning, Damian B van Rossum, Luke Whitesell, Yanmei Huang, Chee Yeun Chung, Valeriya Baru, Sofia Zaichick, Paola Picotti, Susan Lindquist
Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa cis-trans proline isomerase FK506-binding protein (FKBP12). Whether calcineurin/FKBP12 represents a native physiologically relevant assembly that occurs in the absence of pharmacological perturbation has remained elusive...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29221171/proteogenomic-analysis-prioritises-functional-single-nucleotide-variants-in-cancer-samples
#4
Shiyong Ma, Ranjeeta Menon, Rebecca C Poulos, Jason W H Wong
Massively parallel DNA sequencing enables the detection of thousands of germline and somatic single nucleotide variants (SNVs) in cancer samples. The functional analysis of these mutations is often carried out through in silico predictions, with further downstream experimental validation rarely performed. Here, we examine the potential of using mass spectrometry-based proteomics data to further annotate the function of SNVs in cancer samples. RNA-seq and whole genome sequencing (WGS) data from Jurkat cells were used to construct a custom database of single amino acid variant (SAAV) containing peptides and identified over 1,000 such peptides in two Jurkat proteomics datasets...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29214152/identification-of-candidate-casein-kinase-2-substrates-in-mitosis-by-quantitative-phosphoproteomics
#5
Scott F Rusin, Mark E Adamo, Arminja N Kettenbach
Protein phosphorylation is a crucial regulatory mechanism that controls many aspects of cellular signaling. Casein kinase 2 (CK2), a constitutively expressed and active kinase, plays key roles in an array of cellular events including transcription and translation, ribosome biogenesis, cell cycle progression, and apoptosis. CK2 is implicated in cancerous transformation and is a therapeutic target in anti-cancer therapy. The specific and selective CK2 ATP competitive inhibitor, CX-4945 (silmitaseratib), is currently in phase 2 clinical trials...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29211935/a-simple-twist-of-phosphate-immunological-synapse-formation-and-t-cell-receptor-signaling-outcome-in-regulatory-t-cells
#6
Talal A Chatila, Raffaele De Palma
Signaling through the T cell receptor (TCR) regulates T cell homeostasis and effector functions. However, a full accounting of the TCR-coupled signaling networks and how their interplay determines specific functional outcomes remains elusive. Of particular interest are efforts over the last years to elucidate distinctive features of TCR signaling in regulatory T cells (Treg) that may account for some of their unique functional attributes as compared to conventional T (Tconv) cells. In this issue of the European Journal of Immunology, van Ham et al...
December 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29209414/quantitative-in-vivo-phosphoproteomics-reveals-reversible-signaling-processes-during-nitrogen-starvation-and-recovery-in-the-biofuel-model-organism-chlamydomonas-reinhardtii
#7
Valentin Roustan, Shiva Bakhtiari, Pierre-Jean Roustan, Wolfram Weckwerth
Background: Nitrogen deprivation and replenishment induces massive changes at the physiological and molecular level in the green alga Chlamydomonas reinhardtii, including reversible starch and lipid accumulation. Stress signal perception and acclimation involves transient protein phosphorylation. This study aims to provide the first experimental phosphoprotein dataset for the adaptation of C. reinhardtii during nitrogen depletion and recovery growth phases and its impact on lipid accumulation...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29209046/cdc7-dbf4-mediated-phosphorylation-of-hsp90-s164-stabilizes-hsp90-hclk2-mrn-complex-to-enhance-atr-atm-signaling-that-overcomes-replication-stress-in-cancer
#8
An Ning Cheng, Chi-Chen Fan, Yu-Kang Lo, Cheng-Liang Kuo, Hui-Chun Wang, I-Hsin Lien, Shu-Yu Lin, Chung-Hsing Chen, Shih Sheng Jiang, I-Shou Chang, Hsueh-Fen Juan, Ping-Chiang Lyu, Alan Yueh-Luen Lee
Cdc7-Dbf4 kinase plays a key role in the initiation of DNA replication and contributes to the replication stress in cancer. The activity of human Cdc7-Dbf4 kinase remains active and acts as an effector of checkpoint under replication stress. However, the downstream targets of Cdc7-Dbf4 contributed to checkpoint regulation and replication stress-support function in cancer are not fully identified. In this work, we showed that aberrant Cdc7-Dbf4 induces DNA lesions that activate ATM/ATR-mediated checkpoint and homologous recombination (HR) DNA repair...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29199152/low-level-hg2-exposure-modulates-the-b-cell-cytoskeletal-phosphoproteome
#9
Nicholas J Carruthers, Allen J Rosenspire, Joseph A Caruso, Paul M Stemmer
Exposure of Wehi-231 B-cells to Hg2+ for 5min resulted in concentration dependent changes in protein phosphorylations. Phosphorylation was quantified using mass spectrometry to analyze TiO2 and anti-pTyr antibody selected phosphopeptides from Wehi-231 digests. The most frequent and largest amplitude responses to Hg2+ exposure were increased phosphorylation although a decrease was observed for 1% of phosphoproteins detected in the untreated cells. A subset of proteins responded with an increase in phosphorylation to Hg2+ exposure at low micromolar concentrations...
November 30, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29197866/proteomic-analysis-reveals-a-new-benefit-of-periodic-mechanical-stress-on-chondrocytes
#10
Zeng Li, Zhen Wang, Shun Xu, Wenwei Liang, Weimin Fan
BACKGROUND/AIMS: In recent years, a variety of studies have been performed to investigate the cellular responses of periodic mechanical stress. In our previous studies, we found that periodic mechanical stress can promote proliferation and matrix synthesis through the integrin beta 1-mediated ERK1/2 pathway, and we used proteomic analysis to detect quantitative changes in chondrocytes under periodic mechanical stress. Despite these results, the effects and mechanisms of periodic mechanical stress are still not fully understood, so in this study we extended our study using phosphoproteomic techniques...
December 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29196456/deep-coverage-tissue-and-cellular-proteomics-revealed-il-1%C3%AE-can-independently-induce-the-secretion-of-tnf-associated-proteins-from-human-synoviocytes
#11
Shengquan Tang, Suyuan Deng, Jiahui Guo, Xing Chen, Wanling Zhang, Yizhi Cui, Yanzhang Luo, Ziqi Yan, Qing-Yu He, Shan Shen, Tong Wang
Synovitis is a key contributor to the inflammatory environment in osteoarthritis (OA) joints. Currently, the biological therapy of OA is not satisfactory in multiple single-target trials on anti-TNF agents, or IL-1 antagonists. Systems biological understanding of the phosphorylation state in OA synovium is warranted to direct further therapeutic strategies. Therefore, in this study, we compared the human synovial phosphoproteome of the OA with the acute joint fracture subjects. We found that OA synovium had significantly more phosphoproteins, and 82 phosphoproteins could only be specifically found in all the OA samples...
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29196224/phosphorylation-of-mig6-negatively-regulates-the-ubiquitination-and-degradation-of-egfr-mutants-in-lung-adenocarcinoma-cell-lines
#12
Gandhi T K Boopathy, Julia Lim Sze Lynn, Sheena Wee, Jayantha Gunaratne, Wanjin Hong
Activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) leads to constitutively active kinase, improves the EGFR stability and promotes malignant transformation in lung adenocarcinoma. Despite the clinical significance, the mechanism by which the increased kinase activity stabilizes the receptor is not completely understood. Using SILAC phosphoproteomic approach, we identify that Mig6 is highly phosphorylated at S256 in EGFR mutants (19del and L858R). Loss of Mig6 contributes to efficient degradation of EGFR wildtype and mutants in lung cancer cells...
November 28, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29191878/the-target-landscape-of-clinical-kinase-drugs
#13
Susan Klaeger, Stephanie Heinzlmeir, Mathias Wilhelm, Harald Polzer, Binje Vick, Paul-Albert Koenig, Maria Reinecke, Benjamin Ruprecht, Svenja Petzoldt, Chen Meng, Jana Zecha, Katrin Reiter, Huichao Qiao, Dominic Helm, Heiner Koch, Melanie Schoof, Giulia Canevari, Elena Casale, Stefania Re Depaolini, Annette Feuchtinger, Zhixiang Wu, Tobias Schmidt, Lars Rueckert, Wilhelm Becker, Jan Huenges, Anne-Kathrin Garz, Bjoern-Oliver Gohlke, Daniel Paul Zolg, Gian Kayser, Tonu Vooder, Robert Preissner, Hannes Hahne, Neeme Tõnisson, Karl Kramer, Katharina Götze, Florian Bassermann, Judith Schlegl, Hans-Christian Ehrlich, Stephan Aiche, Axel Walch, Philipp A Greif, Sabine Schneider, Eduard Rudolf Felder, Juergen Ruland, Guillaume Médard, Irmela Jeremias, Karsten Spiekermann, Bernhard Kuster
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments...
December 1, 2017: Science
https://www.readbyqxmd.com/read/29191787/post-translational-regulation-of-metabolism-in-fumarate-hydratase-deficient-cancer-cells
#14
Emanuel Gonçalves, Marco Sciacovelli, Ana S H Costa, Maxine Gia Binh Tran, Timothy Isaac Johnson, Daniel Machado, Christian Frezza, Julio Saez-Rodriguez
Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes...
November 27, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29186685/noncanonical-pathway-for-regulation-of-ccl2-expression-by-an-mtorc1-foxk1-axis-promotes-recruitment-of-tumor-associated-macrophages
#15
Hirokazu Nakatsumi, Masaki Matsumoto, Keiichi I Nakayama
C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)-κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29183913/spectral-library-based-analysis-of-arginine-phosphorylations-in-staphylococcus-aureus
#16
Sabryna Junker, Sandra Maaß, Andreas Otto, Stephan Michalik, Friedrich Morgenroth, Ulf Gerth, Michael Hecker, Dörte Becher
Reversible protein phosphorylation is one of the major mechanisms in the regulation of protein expression and protein activity, controlling physiological functions of the important human pathogen Staphylococcus aureus. Phosphorylations at serine, threonine and tyrosine are known to influence for example protein activity in central metabolic pathways and the more energy-rich phosphorylations at histidine, aspartate or cysteine can be found as part of two component system sensor domains or mediating bacterial virulence...
November 28, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29183128/performance-evaluation-of-the-q-exactive-hf-x-for-shotgun-proteomics
#17
Christian D Kelstrup, Dorte B Bekker-Jensen, Tabiwang N Arrey, Alexander Hogrebe, Alexander Harder, Jesper V Olsen
Progress in proteomics is mainly driven by advances in mass spectrometric (MS) technologies. Here we benchmarked the performance of the latest MS instrument in the benchtop Orbitrap series, the Q Exactive HF-X, against its predecessor for proteomics applications. A new peak picking algorithm, a brighter ion source and optimized ion transfers enable productive MS/MS acquisition above 40 Hz at 7500 resolution. The hardware and software improvements collectively resulted in improved peptide and protein identifications across all comparable conditions, with an increase of up to fifty percent at short LC-MS gradients, yielding identification rates of more than one thousand unique peptides per minute...
November 29, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29176673/phosphoproteomics-of-camp-signaling-of-bordetella-adenylate-cyclase-toxin-in-mouse-dendritic-cells
#18
Jakub Novák, Ivo Fabrik, Irena Linhartová, Marek Link, Ondřej Černý, Jiří Stulík, Peter Šebo
The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αMβ2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175091/phosphoprotein-dige-profiles-reflects-blast-differentiation-cytogenetic-risk-stratification-flt3-npm1-mutations-and-therapy-response-in-acute-myeloid-leukaemia
#19
Rakel Brendsdal Forthun, Elise Aasebø, Josef Daniel Rasinger, Siv Lise Bedringaas, Frode Berven, Frode Selheim, Øystein Bruserud, Bjørn Tore Gjertsen
Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by a distinct block in differentiation of myeloid progenitors, recurrent chromosomal translocations and gene mutations of which >50% involve signal transduction through dysregulated kinases and phosphatases. In search for novel protein biomarkers for disease stratification we investigated the phosphoproteome in leukaemic cells from 62 AML patients at time of diagnosis using immobilized metal-affinity chromatography, protein separation by two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry before validation by selected reaction monitoring (SRM)...
November 21, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29169105/constitutive-redox-and-phosphoproteome-changes-in-multiple-herbicide-resistant-avena-fatua-l-are-similar-to-those-of-systemic-acquired-resistance-and-systemic-acquired-acclimation
#20
Erin E Burns, Barbara K Keith, Mohammed Y Refai, Brian Bothner, William E Dyer
Plants are routinely confronted with numerous biotic and abiotic stressors, and in response have evolved highly effective strategies of systemic acquired resistance (SAR) and systemic acquired acclimation (SAA), respectively. A much more evolutionarily recent abiotic stress is the application of herbicides to control weedy plants, and their intensive use has selected for resistant weed populations that cause substantial crop yield losses and increase production costs. Non-target site resistance (NTSR) to herbicides is rapidly increasing worldwide and is associated with alterations in generalized stress defense networks...
November 20, 2017: Journal of Plant Physiology
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