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https://www.readbyqxmd.com/read/28432080/npm1-directs-piddosome-dependent-caspase-2-activation-in-the-nucleolus
#1
Kiyohiro Ando, Melissa J Parsons, Richa B Shah, Chloé I Charendoff, Sheré L Paris, Peter H Liu, Sara R Fassio, Brittany A Rohrman, Ruth Thompson, Andrew Oberst, Samuel Sidi, Lisa Bouchier-Hayes
The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28428870/gene-expression-profiling-during-the-embryo-to-larva-transition-in-the-giant-red-sea-urchin-mesocentrotus-franciscanus
#2
Juan Diego Gaitán-Espitia, Gretchen E Hofmann
In echinoderms, major morphological transitions during early development are attributed to different genetic interactions and changes in global expression patterns that shape the regulatory program for the specification of embryonic territories. In order more thoroughly to understand these biological and molecular processes, we examined the transcriptome structure and expression profiles during the embryo-to-larva transition of a keystone species, the giant red sea urchin Mesocentrotus franciscanus. Using a de novo assembly approach, we obtained 176,885 transcripts from which 60,439 (34%) had significant alignments to known proteins...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28419593/protein-sumoylation-and-phosphorylation-intersect-in-arabidopsis-signaling
#3
Ella Nukarinen, Konstantin Tomanov, Ionida Ziba, Wolfram Weckwerth, Andreas Bachmair
Conjugation of the small ubiquitin-related modifier SUMO to protein substrates impacts on stress responses and on development. We analyzed the proteome and phosphoproteome of mutants in this pathway. Mutants chosen had defects in SUMO ligase SIZ1, which catalyzes attachment of single SUMO moieties onto substrates, and in ligases PIAL1 and 2, which are known to form SUMO chains. 2657 proteins and 550 phosphopeptides were identified and quantified. Approximately 40% of the proteins and 20% of the phosphopeptides showed abundance differences in at least one of the analyzed genotypes, demonstrating the influence of SUMO conjugation on protein abundance and phosphorylation...
April 17, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28411274/posterior-orbitofrontal-and-anterior-cingulate-pathways-to-the-amygdala-target-inhibitory-and-excitatory-systems-with-opposite-functions
#4
Basilis Zikopoulos, Malin Hoistad, Yohan John, Helen Barbas
The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys we found that the anterior cingulate cortex (ACC) innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28409471/study-of-peroxisomal-protein-phosphorylation-by-functional-proteomics
#5
Andreas Schummer, Sven Fischer, Silke Oeljeklaus, Bettina Warscheid
Reversible protein phosphorylation is a frequently occurring posttranslational modification mediated by protein kinases and phosphatases that plays an essential role in the regulation of a large number of cellular processes. Evidence is accumulating that protein phosphorylation is also an important mechanism governing processes associated with peroxisome biology. For an improved and detailed understanding of these processes and their regulation it is therefore crucial to study phosphorylation of peroxisome-associated proteins and to determine the phosphorylated amino acid(s)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28408662/the-gdnf-responsive-phosphoprotein-landscape-identifies-raptor-phosphorylation-required-for-spermatogonial-progenitor-cell-proliferation
#6
Min Wang, Yueshuai Guo, Mei Wang, Tao Zhou, Yuanyuan Xue, Guihua Du, Xiang Wei, Jing Wang, Lin Qi, Hao Zhang, Lufan Li, Lan Ye, Xuejiang Guo, Xin Wu
Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including stem cells support life-long spermatogenesis and male fertility, but pivotal phosphorylation events that regulate fate decisions in SPCs remain unresolved. Here, we described a quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of SPCs following sustained stimulation with glial cell-derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC proliferation...
April 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28408431/molecular-basis-for-the-interaction-between-stress-inducible-phosphoprotein-1-stip1-and-s100a1
#7
Andrzej Maciejewski, Vania F Prado, Marco A M Prado, Wing-Yiu Choy
Stress-inducible phosphoprotein 1 (STIP1) is a cellular co-chaperone, which regulates Hsp70 and Hsp90 activity during client protein folding. Members of the S100-family of dimeric calcium binding proteins have been found to inhibit Hsp association with STIP1 through binding of STIP1 tetratricopeptide repeat (TPR) domains, possibly regulating the chaperone cycle. Here we investigated the molecular basis of S100A1 binding to STIP1. We show that three S100A1 dimers associate with one molecule of STIP1 in a calcium-dependent manner...
April 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#8
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28402964/set-mediates-tce-induced-liver-cell-apoptosis-through-dephosphorylation-and-upregulation-of-nucleolin
#9
Xiaohu Ren, Xinfeng Huang, Xifei Yang, Yungang Liu, Wei Liu, Haiyan Huang, Desheng Wu, Fei Zou, Jianjun Liu
Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402877/structural-basis-for-the-14-3-3-protein-dependent-inhibition-of-phosducin-function
#10
Miroslava Kacirova, Jiri Novacek, Petr Man, Veronika Obsilova, Tomas Obsil
Phosducin (Pdc) is a conserved phosphoprotein that, when unphosphorylated, binds with high affinity to the complex of βγ-subunits of G protein transducin (Gtβγ). The ability of Pdc to bind to Gtβγ is inhibited through its phosphorylation at S54 and S73 within the N-terminal domain (Pdc-ND) followed by association with the scaffolding protein 14-3-3. However, the molecular basis for the 14-3-3-dependent inhibition of Pdc binding to Gtβγ is unclear. By using small-angle x-ray scattering, high-resolution NMR spectroscopy, and limited proteolysis coupled with mass spectrometry, we show that phosphorylated Pdc and 14-3-3 form a complex in which the Pdc-ND region 45-80, which forms a part of Pdc's Gtβγ binding surface and contains both phosphorylation sites, is restrained within the central channel of the 14-3-3 dimer, with both 14-3-3 binding motifs simultaneously participating in protein association...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28396341/bioactivity-of-oral-linaclotide-in-human-colorectum-for-cancer-chemoprevention
#11
David S Weinberg, Jieru E Lin, Nathan R Foster, Gary J Della'Zanna, Asad Umar, Drew K Seisler, Walter K Kraft, David M Kastenberg, Leo C Katz, Paul J Limburg, Scott A Waldman
Guanylate cyclase C (GUCY2C) is a tumor suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined...
April 10, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28394227/ribosomal-p-antibody-30-years-on-the-road
#12
V T Viana, L Durcan, E Bonfa, K B Elkon
The identity of the protein antigens targeted by anti-cytoplasmic antibodies in lupus was discovered 30 years ago. These antigens are three acidic ribosomal phosphoproteins, P0, P1, and P2. Precise identification of the shared epitope on these three proteins enabled sensitive and specific immunoassays to be developed. Anti-P antibodies are highly specific for systemic lupus erythematosus (SLE) and occur in 15%-35% of patients, depending on ethnicity as well as the age of onset. Increased frequencies of detection of anti-P have been reported in childhood SLE as well as in neuropsychiatric, renal, and hepatic disease...
April 2017: Lupus
https://www.readbyqxmd.com/read/28392386/phosphoprotein-chitosan-electrospun-nanofibrous-scaffold-for-biomineralization
#13
Hongshan Liang, Feng Sheng, Bin Zhou, Yaqiong Pei, Bin Li, Jing Li
In this study, negatively charged phosvitin (PV) and positively charged chitosan (CS) were alternately deposited on negatively charged cellulose mats via layer-by-layer (LBL) self-assembly technique. Morphologies of the LBL films coating mats were observed by scanning electron microscope (SEM). Afterwards, in vitro biomimetic mineralization was carried out through incubation of the fibrous mats in a simulated body fluid (SBF) solution for different time. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) were used to characterize the morphology and structure of the deposited mineral phase on the scaffolds...
April 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28388507/novel-protein-kinase-targets-in-vascular-smooth-muscle-therapeutics
#14
REVIEW
David A Tulis
Many signaling factors have been identified over the years that serve as mechanistic foundations for the pathogenesis and/or maintenance of cardiovascular disease (CVD). Of these, cyclic nucleotide-driven protein kinases in vascular smooth muscle (VSM) are of essential importance. Comprised primarily of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, these ubiquitous signaling molecules have capacity to operate through numerous downstream effectors including vasodilator-stimulated phosphoprotein (VASP) to control aberrant VSM growth elemental to CVD...
April 4, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28387646/unfair-competition-governs-the-interaction-of-pcpi-17-with-myosin-phosphatase-pp1-mypt1
#15
Joshua J Filter, Byron C Williams, Masumi Eto, David Shalloway, Michael L Goldberg
The small phosphoprotein pCPI-17 inhibits myosin light chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MCLP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site...
April 7, 2017: ELife
https://www.readbyqxmd.com/read/28387456/synonymous-codon-usage-of-genes-in-polymerase-complex-of-newcastle-disease-virus
#16
Chandra Shekhar Kumar, Sachin Kumar
Newcastle disease virus (NDV) is pathogenic to both avian and non-avian species but extensively finds poultry as its primary host and causes heavy economic losses in the poultry industry. In this study, a total of 186 polymerase complex comprising of nucleoprotein (N), phosphoprotein (P), and large polymerase (L) genes of NDV was analyzed for synonymous codon usage. The relative synonymous codon usage and effective number of codons (ENC) values were used to estimate codon usage variation in each gene. Correspondence analysis (COA) was used to study the major trend in codon usage variation...
April 7, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/28383256/phosphoproteomics-with-activated-ion-electron-transfer-dissociation
#17
Nicholas M Riley, Alexander S Hebert, Gerhard Dürnberger, Florian Stanek, Karl Mechtler, Michael S Westphall, Joshua J Coon
The ability to localize phosphosites to specific amino acid residues is crucial to translating phosphoproteomic data into biological meaningful contexts. In a companion manuscript ( Anal. Chem. 2017 , DOI: 10.1021/acs.analchem.7b00213 ), we described a new implementation of activated ion electron transfer dissociation (AI-ETD) on a quadrupole-Orbitrap-linear ion trap hybrid MS system (Orbitrap Fusion Lumos), which greatly improved peptide fragmentation and identification over ETD and other supplemental activation methods...
April 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28382632/a-phosphoproteomic-landscape-of-rice-oryza-sativa-tissues
#18
Yifeng Wang, Xiaohong Tong, Jiehua Qiu, Zhiyong Li, Juan Zhao, Yuxuan Hou, Liqun Tang, Jian Zhang
Protein phosphorylation is an important post-translational modification that regulates various plant developmental processes. Here, we report a comprehensive, quantitative phosphoproteomic profile of six rice tissues, including callus, leaf, root, shoot meristem, young panicle and mature panicle from Nipponbare by employing a MS-based, label-free approach. A total of 7171 unique phosphorylation sites in 4792 phosphopeptides from 2657 phosphoproteins were identified, including 4613 peptides were differentially phosphorylated among the tissues...
April 5, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28381545/drug-resistance-mechanisms-in-colorectal-cancer-dissected-with-cell-type-specific-dynamic-logic-models
#19
Federica Eduati, Victoria Doldàn-Martelli, Bertram Klinger, Thomas Cokelaer, Anja Sieber, Fiona Kogera, Mathurin Dorel, Mathew J Garnett, Nils Blüthgen, Julio Saez-Rodriguez
Genomic features are used as biomarkers of sensitivity to kinase inhibitors used widely to treat human cancer, but effective patient stratification based on these principles remains limited in impact. Insofar as kinase inhibitors interfere with signaling dynamics, and, in turn, signaling dynamics affects inhibitor responses, we investigated associations in this study between cell-specific dynamic signaling pathways and drug sensitivity. Specifically, we measured 14 phosphoproteins under 43 different perturbed conditions (combinations of 5 stimuli and 7 inhibitors) in 14 colorectal cancer cell lines, building cell line-specific dynamic logic models of underlying signaling networks...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28376489/triiodothyronine-potentiates-vasorelaxation-via-pkg-vasp-signaling-in-vascular-smooth-muscle-cells
#20
Sherin Samuel, Kuo Zhang, Yi-Da Tang, A Martin Gerdes, Maria Alicia Carrillo-Sepulveda
BACKGROUND/AIMS: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. METHODS: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours)...
April 4, 2017: Cellular Physiology and Biochemistry
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