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https://www.readbyqxmd.com/read/29145615/iptmnet-an-integrated-resource-for-protein-post-translational-modification-network-discovery
#1
Hongzhan Huang, Cecilia N Arighi, Karen E Ross, Jia Ren, Gang Li, Sheng-Chih Chen, Qinghua Wang, Julie Cowart, K Vijay-Shanker, Cathy H Wu
Protein post-translational modifications (PTMs) play a pivotal role in numerous biological processes by modulating regulation of protein function. We have developed iPTMnet (http://proteininformationresource.org/iPTMnet) for PTM knowledge discovery, employing an integrative bioinformatics approach-combining text mining, data mining, and ontological representation to capture rich PTM information, including PTM enzyme-substrate-site relationships, PTM-specific protein-protein interactions (PPIs) and PTM conservation across species...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29142207/phosphorylation-dynamics-dominate-the-regulated-proteome-during-early-xenopus-development
#2
Elizabeth H Peuchen, Olivia F Cox, Liangliang Sun, Alex S Hebert, Joshua J Coon, Matthew M Champion, Norman J Dovichi, Paul W Huber
The earliest stages of animal development are largely controlled by changes in protein phosphorylation mediated by signaling pathways and cyclin-dependent kinases. In order to decipher these complex networks and to discover new aspects of regulation by this post-translational modification, we undertook an analysis of the X. laevis phosphoproteome at seven developmental stages beginning with stage VI oocytes and ending with two-cell embryos. Concurrent measurement of the proteome and phosphoproteome enabled measurement of phosphosite occupancy as a function of developmental stage...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141230/sub-minute-phosphoregulation-of-cell-cycle-systems-during-plasmodium-gamete-formation
#3
Brandon M Invergo, Mathieu Brochet, Lu Yu, Jyoti Choudhary, Pedro Beltrao, Oliver Billker
The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This revealed an unexpectedly broad response, with proteins related to distinct cell cycle events undergoing simultaneous phosphoregulation...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29136244/a-molecular-cascade-modulates-map1b-and-confers-resistance-to-mtor-inhibition-in-human-glioblastoma
#4
Dan R Laks, Juan A Oses-Prieto, Alvaro G Alvarado, Jonathan Nakashima, Shreya Chand, Daniel B Azzam, Ankur A Gholkar, Jantzen Sperry, Kirsten Ludwig, Michael C Condro, Serli Nazarian, Anjelica Cardenas, Michelle Y S Shih, Robert Damoiseaux, Bryan France, Nicholas Orozco, Koppany Visnyei, Thomas J Crisman, Fuying Gao, Jorge Z Torres, Giovanni Coppola, Alma L Burlingame, Harley I Kornblum
Background: Clinical trials of therapies directed against nodes of the PI3K/AKT/mTOR signaling axis in Glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin and our analysis implicated a role for GSK3B attenuation in mediating resistance that was confirmed by functional studies...
November 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29124795/proteomic-analysis-of-lysine-acetylation-provides-strong-evidence-for-acetylated-proteins-involved-in-plant-meiosis-and-tapetum-function
#5
Xiaojing Li, Juanying Ye, Hong Ma, Pingli Lu
Protein lysine acetylation (KAC) is a dynamic and reversible post-translational modification, playing important biological roles in many organisms. Although KAC was shown to affect reproductive development and meiosis in yeast and animals, similar studies are largely lacking in flowering plants, especially in a proteome-scale investigation for a certain reproductive stage. Here, we reported results from a proteomic investigation to detect KAC status of the developing rice anthers near the time of meiosis (RAM), providing strong biochemical evidence for roles of many KAC-affected proteins during rice anther development and meiosis...
November 10, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29119230/re-evaluation-of-protein-kinase-ck2-pleiotropy-new-insights-provided-by-a-phosphoproteomics-analysis-of-ck2-knockout-cells
#6
Cinzia Franchin, Christian Borgo, Luca Cesaro, Silvia Zaramella, Jordi Vilardell, Mauro Salvi, Giorgio Arrigoni, Lorenzo A Pinna
CK2 denotes a ubiquitous and pleiotropic protein kinase whose holoenzyme is composed of two catalytic (α and/or α') and two regulatory β subunits. The CK2 consensus sequence, S/T-x-x-D/E/pS/pT is present in numerous phosphosites, but it is not clear how many of these are really generated by CK2. To gain information about this issue, advantage has been taken of C2C12 cells entirely deprived of both CK2 catalytic subunits by the CRISPR/Cas9 methodology. A comparative SILAC phosphoproteomics analysis reveals that, although about 30% of the quantified phosphosites do conform to the CK2 consensus, only one-third of these are substantially reduced in the CK2α/α'((-/-)) cells, consistent with their generation by CK2...
November 9, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29116813/tio2-with-tandem-fractionation-taft-an-approach-for-rapid-deep-reproducible-and-high-throughput-phosphoproteome-analysis
#7
Liangliang Ren, Chaoying Li, Wenli Shao, Weiran Lin, Fuchu He, Ying Jiang
Mass-spectrometry-based phosphoproteomic workflows traditionally require efficient prefractionation and enrichment of phosphopeptides to gain an in-depth, global, and unbiased systematic investigation of phosphoproteome. Here we present TiO2 with tandem fractionation (TAFT) approach, which combines titanium dioxide (TiO2) enrichment and tandem high-pH reverse-phase (HpRP) for phosphoproteome analysis in a high-throughput manner; the entire workflow takes only 3 h to complete without laborious phosphopeptide preparation...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29113996/characterization-of-the-molecular-mechanisms-underlying-glucose-stimulated-insulin-secretion-from-isolated-pancreatic-%C3%AE-cells-using-ptmomics
#8
Taewook Kang, Pia Jensen, Honggang Huang, Gitte Lund Christensen, Nils Billestrup, Martin R Larsen
Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. However, the molecular mechanisms underlying the insulin secretion are unclear. Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins...
November 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29101250/phosphoproteomics-links-glycogen-synthase-kinase-3-to-rna-splicing
#9
Le Tran Phuc Khoa, Yali Dou
Protein kinases play essential biological roles by phosphorylating a diverse range of signaling molecules, but deciphering their direct physiological targets remains a challenge. A new study by Shinde et al. uses phosphoproteomics to identify glycogen synthase kinase-3 (GSK-3) substrates in mouse embryonic stem cells (mESCs), providing a broad profile of GSK-3 activity and defining a new role for this central kinase in regulating RNA splicing.
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29094114/recent-advances-in-phosphoproteomics-and-application-to-neurological-diseases
#10
REVIEW
Justine V Arrington, Chuan-Chih Hsu, Sarah G Elder, W Andy Tao
Phosphorylation has an incredible impact on the biological behavior of proteins, altering everything from intrinsic activity to cellular localization and complex formation. It is no surprise then that this post-translational modification has been the subject of intense study and that, with the advent of faster, more accurate instrumentation, the number of large-scale mass spectrometry-based phosphoproteomic studies has swelled over the past decade. Recent developments in sample preparation, phosphorylation enrichment, quantification, and data analysis strategies permit both targeted and ultra-deep phosphoproteome profiling, but challenges remain in pinpointing biologically relevant phosphorylation events...
November 2, 2017: Analyst
https://www.readbyqxmd.com/read/29083192/tip-based-fractionation-of-batch-enriched-phosphopeptides-facilitates-easy-and-robust-phosphoproteome-analysis
#11
Alireza Dehghani, Markus Gödderz, Dominic Winter
The identification of large numbers of phosphopeptides from complex samples largely relies on sample fractionation to reduce complexity and allow using large amounts of starting material. For such experiments, commonly fractionation of whole cell lysate digests followed by enrichment of phosphopeptides from the single fractions is performed. We evaluated the tip-based fractionation of batch-enriched phosphopeptides as an alternative method. We compared three tip-based fractionation methods employing strong cation exchange (SCX), strong anion exchange (SAX), and C18 material for basic reversed-phase (BRP) fractionation using HeLa whole cell lysate digests...
November 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29083189/sh2-superbinder-modified-monolithic-capillary-column-for-the-sensitive-analysis-of-protein-tyrosine-phosphorylation
#12
Yating Yao, Yangyang Bian, Mingming Dong, Yan Wang, Jiawen Lv, Lianfang Chen, Hongwei Wang, Jiawei Mao, Jing Dong, Mingliang Ye
In this study, we present a method to specifically capture phosphotyrosine (pTyr) peptides from minute amount of sample for the sensitive analysis of protein tyrosine phosphorylation. We immobilized SH2 superbinder on a monolithic capillary column to construct a microreactor to enrich pTyr peptides. It was found that the synthetic pTyr peptide could be specifically enriched by the microreactor from the peptide mixture prepared by spiking of the synthetic pTyr peptide into the tryptic digests of α-casein and β-casein with molar ratios of 1:1000:1000...
November 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29077858/proteomics-and-phosphoproteomics-in-precision-medicine-applications-and-challenges
#13
Girolamo Giudice, Evangelia Petsalaki
Recent advances in proteomics allow the accurate measurement of abundances for thousands of proteins and phosphoproteins from multiple samples in parallel. Therefore, for the first time, we have the opportunity to measure the proteomic profiles of thousands of patient samples or disease model cell lines in a systematic way, to identify the precise underlying molecular mechanism and discover personalized biomarkers, networks and treatments. Here, we review examples of successful use of proteomics and phosphoproteomics data sets in as well as their integration other omics data sets with the aim of precision medicine...
October 25, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29064675/age-dependent-effects-of-acute-alcohol-administration-in-the-hippocampal-phosphoproteome
#14
Ana Contreras, Lidia Morales, Ali Tebourbi, Miguel Miguéns, Nuria Del Olmo, Carmen Pérez-García
Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration...
November 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29063176/evaluation-of-protein-phosphorylation-in-bull-sperm-during-their-maturation-in-the-epididymis
#15
Jana Jankovičová, Katarína Michalková, Petra Sečová, Ľubica Horovská, Pavla Maňásková-Postlerová, Jana Antalíková
Phosphorylation, or dephosphorylation, is one of the most frequent post-translational modifications regulating protein-protein activity in eukaryotic cells. Whereas mature spermatozoa (as specialized cells) are transcriptionally inactive and do not synthesize new proteins, phosphorylation of sperm proteins is very important for the regulation of the sperm function. Although the post-testicular maturation of spermatozoa is a process common to all mammals, comparative studies showed significant differences in sperm surface proteins and the mechanisms of protein modification during the epididymal maturation...
October 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29061642/multilayered-omics-based-analysis-of-a-head-and-neck-cancer-model-of-cisplatin-resistance-reveals-intratumoral-heterogeneity-and-treatment-induced-clonal-selection
#16
Franziska Niehr, Theresa Eder, Tanja Pilz, Robert Konschak, Denise Treue, Frederick Klauschen, Michael Bockmayr, Seval Türkmen, Korinna Jöhrens, Volker Budach, Ingeborg Tinhofer
PURPOSE: Platinum-based drugs, in particular cisplatin (CDDP), are used for treatment of squamous cell carcinoma of the head and neck (SCCHN). Despite initial responses, CDDP treatment often results in chemoresistance, leading to therapeutic failure. The role of primary resistance at subclonal level and treatment-induced clonal selection in the development of CDDP resistance remains unknown. EXPERIMENTAL DESIGN: By applying targeted next-generation sequencing, fluorescence in-situ hybridization, microarray-based transcriptome and mass spectrometry-based phosphoproteome analysis to the CDDP-sensitive SCCHN cell line FaDu, a CDDP-resistant subline and single-cell derived subclones, the molecular basis of CDDP resistance was elucidated...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29058706/histidine-kinases-and-the-missing-phosphoproteome-from-prokaryotes-to-eukaryotes
#17
Kevin Adam, Tony Hunter
Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell's proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29058608/in-vivo-phosphoproteome-characterization-reveals-key-starch-granule-binding-phosphoproteins-involved-in-wheat-water-deficit-response
#18
Guan-Xing Chen, Shou-Min Zhen, Yan-Lin Liu, Xing Yan, Ming Zhang, Yue-Ming Yan
BACKGROUND: Drought stress during grain development causes significant yield loss in cereal production. The phosphorylated modification of starch granule-binding proteins (SGBPs) is an important mechanism regulating wheat starch biosynthesis. In this study, we performed the first proteomics and phosphoproteomics analyses of SGBPs in elite Chinese bread wheat (Triticum aestivum L.) cultivar Jingdong 17 under well-watered and water-stress conditions. RESULTS: Water stress treatment caused significant reductions in spike grain numbers and weight, total starch and amylopectin content, and grain yield...
October 23, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29046388/the-early-dendritic-cell-signaling-induced-by-virulent-francisellatularensis-strain-occurs-in-phases-and-involves-the-activation-of-erks-and-p38-in-the-later-stage
#19
Ivo Fabrik, Marek Link, Daniela Putzova, Lenka Plzakova, Zuzana Lubovska, Vlada Philimonenko, Ivona Pavkova, Pavel Rehulka, Zuzana Krocova, Pavel Hozak, Marina Santic, Jiri Stulik
Dendritic cells (DCs) infected by Francisella tularensis are poorly activated and do not undergo classical maturation process. While reasons of such unresponsiveness are not fully understood, their impact on the priming of immunity is well appreciated. Previous attempts to explain the behavior of Francisella-infected DCs were hypothesis-driven and focused on events at later stages of infection. Here, we took an alternative unbiased approach by applying methods of global phosphoproteomics to analyze the dynamics of cell signaling in primary DCs during the first hour of infection by Francisella tularensis...
October 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29043805/mitogen-activated-protein-kinase-kinase-5-regulates-proliferation-and-biosynthetic-processes-in-procyclic-forms-of-trypanosoma-brucei
#20
Fernanda G Kugeratski, Michel Batista, Carla V de Paula Lima, Lisa J Neilson, Elizabeth Sousa da Cunha, Lyris M de Godoy, Sara Zanivan, Marco A Krieger, Fabricio K Marchini
The pathogenic protozoan T. brucei alternates into distinct developmental stages in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK) signaling pathways transduce extracellular stimuli into a range of cellular responses, which ultimately lead to the adaptation to the external environment. Here, we combined a loss of function approach with stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T...
November 7, 2017: Journal of Proteome Research
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