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phosphoproteomics

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https://www.readbyqxmd.com/read/27903807/concerted-changes-in-the-phosphoproteome-and-metabolome-under-different-co2-o2-gaseous-conditions-in-arabidopsis-rosettes
#1
Cyril Abadie, Samuel Mainguet, Marlène Davanture, Michael Hodges, Michel Zivy, Guillaume Tcherkez
Considerable efforts are currently devoted to understanding the regulation of primary carbon metabolism in plant leaves, which is known to change dramatically with environmental conditions, e.g. during light/dark transitions. Protein phosphorylation is believed to be a key factor in such a metabolic control. In fact, some studies have suggested modifications in the phosphorylation status of key enzymes in the dark compared with the light, or when photosynthesis varies. However, a general view of the phosphoproteome and reciprocal alterations in both the phosphoproteome and metabolome under a wide spectrum of CO2 and O2 conditions so as to vary both gross photosynthesis and photorespiration is currently lacking...
July 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27903465/label-free-quantitative-phosphoproteomic-profiling-of-cellular-response-induced-by-an-insect-cytokine-paralytic-peptide
#2
Liang Song, Fei Wang, Zhaoming Dong, Xiaoting Hua, Qingyou Xia
: Paralytic peptide (PP) participates in diverse physiological processes as an insect cytokine, such as immunity control, paralysis induction, regulation of cell morphology and proliferation. To investigate the molecular mechanism underlying those physiological activities, we systematically investigated the global phosphorylation events in fat body of silkworm larvae induced by PP through label-free quantitative phosphoproteomics. 2534 phosphosites were finally identified, of which the phosphorylation level of 620 phosphosites on 244 proteins was significantly up-regulated and 67 phosphosites on 43 proteins was down-regulated...
November 26, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27902967/the-non-receptor-tyrosine-kinase-tnk2-ack1-is-a-novel-therapeutic-target-in-triple-negative-breast-cancer
#3
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S Kelkar, Mustafa A Bharbuiya, Pamela L Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P Mahajan, Akhilesh Pandey
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899381/castration-resistance-in-prostate-cancer-is-mediated-by-the-kinase-nek6
#4
Atish D Choudhury, Anna C Schinzel, Maura B Cotter, Rosina T Lis, Katherine Labella, Ying Jie Lock, Francesca Izzo, Isil Guney, Michaela Bowden, Yvonne Y Li, Jinal Patel, Emily Hartman, Steven A Carr, Monica Schenone, Jacob D Jaffe, Philip W Kantoff, Peter S Hammerman, William C Hahn
In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27888141/a-glimpse-into-the-modulation-of-post-translational-modifications-of-human-colonizing-bacteria
#5
REVIEW
Paulo André Dias Bastos, João Pinto da Costa, Rui Vitorino
Protein post-translational modifications (PTMs) are a key bacterial feature that holds the capability to modulate protein function and responses to environmental cues. Until recently, their role in the regulation of prokaryotic systems has been largely neglected. However, the latest developments in mass spectrometry-based proteomics have allowed an unparalleled identification and quantification of proteins and peptides that undergo PTMs in bacteria, including in species which directly or indirectly affect human health...
November 22, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27881952/tissue-type-plasminogen-activator-tpa-modulates-the-postsynaptic-response-of-cerebral-cortical-neurons-to-the-presynaptic-release-of-glutamate
#6
Valerie Jeanneret, Fang Wu, Paola Merino, Enrique Torre, Ariel Diaz, Lihong Cheng, Manuel Yepes
Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27877176/the-arabidopsis-tor-kinase-specifically-regulates-the-expression-of-nuclear-genes-coding-for-plastidic-ribosomal-proteins-and-the-phosphorylation-of-the-cytosolic-ribosomal-protein-s6
#7
Thomas Dobrenel, Eder Mancera-Martínez, Céline Forzani, Marianne Azzopardi, Marlène Davanture, Manon Moreau, Mikhail Schepetilnikov, Johana Chicher, Olivier Langella, Michel Zivy, Christophe Robaglia, Lyubov A Ryabova, Johannes Hanson, Christian Meyer
Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27862258/raine-syndrome-omim-259775-caused-by-fam20c-mutation-is-congenital-sclerosing-osteomalacia-with-cerebral-calcification-omim-259660
#8
Michael P Whyte, William H McAlister, Michael D Fallon, Mary Ella Pierpont, Vinieth N Bijanki, Shenghui Duan, Ghada A Otaify, William S Sly, Steven Mumm
In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, "Raine syndrome" entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775)...
November 10, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27834733/quantitative-proteomics-reveals-fundamental-regulatory-differences-in-oncogenic-hras-and-idh1-driven-astrocytoma
#9
Sophia Doll, Anatoly Urisman, Juan A Oses-Prieto, David Arnott, Alma L Burlingame
Glioblastoma multiformes (GBMs) are high-grade astrocytomas and the most common brain malignancies. Primary GBMs are often associated with disturbed RAS signaling, and expression of oncogenic HRAS results in a malignant phenotype in glioma cell lines. Secondary GBMs arise from lower-grade astrocytomas, have slower progression than primary tumors, and contain IDH1 mutations in over 70% of cases. Despite significant amount of accumulating genomic and transcriptomic data, the fundamental mechanistic differences of gliomagenesis in these two types of high-grade astrocytoma remain poorly understood...
November 10, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27821169/a-new-tool-for-the-chemical-genetic-investigation-of-the-plasmodium-falciparum-pfnek-2-nima-related-kinase
#10
Deborah F Mitcheson, Andrew R Bottrill, Katherine Carr, Christopher R Coxon, Celine Cano, Bernard T Golding, Roger J Griffin, Andrew M Fry, Christian Doerig, Richard Bayliss, Andrew B Tobin
BACKGROUND: Examining essential biochemical pathways in Plasmodium falciparum presents serious challenges, as standard molecular techniques such as siRNA cannot be employed in this organism, and generating gene knock-outs of essential proteins requires specialized conditional approaches. In the study of protein kinases, pharmacological inhibition presents a feasible alternative option. However, as in mammalian systems, inhibitors often lack the desired selectivity. Described here is a chemical genetic approach to selectively inhibit Pfnek-2 in P...
November 7, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27818261/phosphorylation-is-a-central-mechanism-for-circadian-control-of-metabolism-and-physiology
#11
Maria S Robles, Sean J Humphrey, Matthias Mann
Circadian clocks are self-sustainable endogenous oscillators, present in virtually every cell, driving daily cycles of metabolism and physiology. The molecular mechanism of the circadian clock is based on interconnected transcriptional and translational feedback loops. While many studies have addressed circadian rhythms of the transcriptome and, to a lesser extent, the proteome, none have investigated the phosphoproteome. We apply mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of circadian phosphorylation in mammals...
October 29, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27818260/nuclear-proteomics-uncovers-diurnal-regulatory-landscapes-in-mouse-liver
#12
Jingkui Wang, Daniel Mauvoisin, Eva Martin, Florian Atger, Antonio Núñes Galindo, Loïc Dayon, Federico Sizzano, Alessio Palini, Martin Kussmann, Patrice Waridel, Manfredo Quadroni, Vjekoslav Dulić, Felix Naef, Frédéric Gachon
Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at the transcriptional level, much less is known about temporally controlled functions within the nucleus and their regulation at the protein level. Here, we quantified the temporal nuclear accumulation of proteins and phosphoproteins from mouse liver by SILAC proteomics...
October 31, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27811184/coupling-an-eml4-alk-centric-interactome-with-rna-interference-identifies-sensitizers-to-alk-inhibitors
#13
Guolin Zhang, Hannah Scarborough, Jihye Kim, Andrii I Rozhok, Yian Ann Chen, Xiaohui Zhang, Lanxi Song, Yun Bai, Bin Fang, Richard Z Liu, John Koomen, Aik Choon Tan, James Degregori, Eric B Haura
Patients with lung cancers harboring anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors, but acquired resistance inevitably arises. A better understanding of proximal ALK signaling mechanisms may identify sensitizers to ALK inhibitors that disrupt the balance between prosurvival and proapoptotic effector signals. Using affinity purification coupled with mass spectrometry in an ALK fusion lung cancer cell line (H3122), we generated an ALK signaling network and investigated signaling activity using tyrosine phosphoproteomics...
October 18, 2016: Science Signaling
https://www.readbyqxmd.com/read/27797916/flux-control-through-protein-phosphorylation-in-yeast
#14
Yu Chen, Jens Nielsen
Protein phosphorylation is one of the most important mechanisms regulating metabolism as it can directly modify metabolic enzymes by the addition of phosphate groups. Attributed to such a rapid and reversible mechanism, cells can adjust metabolism rapidly in response to temporal changes. The yeast Saccharomyces cerevisiae, a widely used cell factory and model organism, is reported to show frequent phosphorylation events in metabolism. Studying protein phosphorylation in S. cerevisiae allow for gaining new insight into the function of regulatory networks, which may enable improved metabolic engineering as well as identify mechanisms underlying human metabolic diseases...
October 25, 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27794612/phosphoproteome-profiling-reveals-molecular-mechanisms-of-growth-factor-mediated-kinase-inhibitor-resistance-in-egfr-overexpressing-cancer-cells
#15
Heiner Koch, Mathias Wilhelm, Benjamin Ruprecht, Scarlet Beck, Martin Frejno, Susan Klaeger, Bernhard Kuster
Although substantial progress has been made regarding the use of molecularly targeted cancer therapies, resistance almost invariably develops and presents a major clinical challenge. The tumor microenvironment can rescue cancer cells from kinase inhibitors by growth factor mediated induction of pro-survival pathways. Here, we show that EGFR inhibition by Gefitinib is counteracted by growth factors notably FGF2 and we assessed the global molecular consequences of this resistance at the proteome and phosphoproteome level in A431 cells...
October 30, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27794539/human-r1441c-lrrk2-regulates-the-synaptic-vesicle-proteome-and-phosphoproteome-in-a-drosophila-model-of-parkinson-s-disease
#16
Shariful Islam, Hendrik Nolte, Wright Jacob, Anna B Ziegler, Stefanie Pütz, Yael Grosjean, Karolina Szczepanowska, Aleksandra Trifunovic, Thomas Braun, Hermann Heumann, Rolf Heumann, Bernhard Hovemann, Darren J Moore, Marcus Krüger
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson's disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model...
October 29, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27790906/study-of-o-phosphorylation-sites-in-proteins-involved-in-photosynthesis-related-processes-in-synechocystis-sp-strain-pcc-6803-application-of-the-srm-approach
#17
Martina Angeleri, Dorota Muth-Pawlak, Eva-Mari Aro, Natalia Battchikova
O-phosphorylation has been shown in photosynthesis-related proteins in a cyanobacterium Synechocystis sp. strain PCC 6803 (thereafter Synechocystis 6803) suggesting that phosphorylation of S,T and Y residues might be important in photosynthesis-related processes. Investigation of biological roles of these phosphorylation events requires confident knowledge of the phosphorylated sites and prospects for their individual assessment. We performed phosphoproteomic analysis of Synechocystis 6803 using TiO2 enrichment of the phosphopeptides followed by LC-MS/MS and discovered 367 phosphorylation sites in 190 proteins participating in various cellular functions...
October 28, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27782176/functional-kinomics-establishes-a-critical-node-of-volume-sensitive-cation-cl-cotransporter-regulation-in-the-mammalian-brain
#18
Jinwei Zhang, Geng Gao, Gulnaz Begum, Jinhua Wang, Arjun R Khanna, Boris E Shmukler, Gerrit M Daubner, Paola de Los Heros, Paul Davies, Joby Varghese, Mohammad Iqbal H Bhuiyan, Jinjing Duan, Jin Zhang, Daniel Duran, Seth L Alper, Dandan Sun, Stephen J Elledge, Dario R Alessi, Kristopher T Kahle
Cell volume homeostasis requires the dynamically regulated transport of ions across the plasmalemma. While the ensemble of ion transport proteins involved in cell volume regulation is well established, the molecular coordinators of their activities remain poorly characterized. We utilized a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-content kinase inhibitor screen, and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr(991)/Thr(1048) phosphorylation - a key signaling event in cell swelling-induced regulatory volume decrease (RVD)...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27775022/proteomic-and-phosphoproteomic-analysis-of-renal-cortex-in-a-salt-load-rat-model-of-advanced-kidney-damage
#19
Shaoling Jiang, Hanchang He, Lishan Tan, Liangliang Wang, Zhengxiu Su, Yufeng Liu, Hongguo Zhu, Menghuan Zhang, Fan Fan Hou, Aiqing Li
Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27774993/knowledge-guided-fuzzy-logic-modeling-to-infer-cellular-signaling-networks-from-proteomic-data
#20
Hui Liu, Fan Zhang, Shital Kumar Mishra, Shuigeng Zhou, Jie Zheng
Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data...
October 24, 2016: Scientific Reports
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