232 results match your criteria phosphoproteomics 2019

SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment.

Cell Metab 2021 May 18. Epub 2021 May 18.

Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA. Electronic address:

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. Read More

View Article and Full-Text PDF

Variable post-translational modifications of SARS-CoV-2 nucleocapsid protein.

Glycobiology 2021 May 13. Epub 2021 May 13.

Complex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), started in 2019 in China and quickly spread into a global pandemic. Nucleocapsid protein (N protein) is highly conserved and the most abundant protein in coronaviruses and thus a potential target for both vaccine and point-of-care diagnostics. N Protein has been suggested in the literature as having post-translational modifications (PTMs), and accurately defining these PTMs is critical for its potential use in medicine. Read More

View Article and Full-Text PDF

Correction: Yagüe, P., et al. Goals and Challenges in Bacterial Phosphoproteomics. 2019, , 5678.

Int J Mol Sci 2020 Dec 9;21(24). Epub 2020 Dec 9.

Área de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain.

The authors wish to make the following corrections to this paper [1]:The author name "Gemma Fernánez-García" should be "Gemma Fernández-García" [... Read More

View Article and Full-Text PDF
December 2020

Footprint-based functional analysis of multiomic data.

Curr Opin Syst Biol 2019 Jun;15:82-90

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute of Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.

Omic technologies allow us to generate extensive data, including transcriptomic, proteomic, phosphoproteomic and metabolomic. These data can be used to study signal transduction, gene regulation and metabolism. In this review, we summarise resources and methods to analysis these types of data. Read More

View Article and Full-Text PDF

The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

Cell 2020 08 28;182(3):685-712.e19. Epub 2020 Jun 28.

Institute for Clinical and Experimental Pharmacology and Toxicology, University of Freiburg, Freiburg 79104, Germany.

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Read More

View Article and Full-Text PDF

Proteomic Investigation Uncovers Potential Targets and Target Sites of Pneumococcal Serine-Threonine Kinase StkP and Phosphatase PhpP.

Front Microbiol 2019 4;10:3101. Epub 2020 Feb 4.

Department of Microbial Proteomics, Institute of Microbiology, University of Greifswald, Greifswald, Germany.

Like eukaryotes, different bacterial species express one or more Ser/Thr kinases and phosphatases that operate in various signaling networks by catalyzing phosphorylation and dephosphorylation of proteins that can immediately regulate biochemical pathways by altering protein function. The human pathogen encodes a single Ser/Thr kinase-phosphatase couple known as StkP-PhpP, which has shown to be crucial in the regulation of cell wall synthesis and cell division. In this study, we applied proteomics to further understand the physiological role of pneumococcal PhpP and StkP with an emphasis on phosphorylation events on Ser and Thr residues. Read More

View Article and Full-Text PDF
February 2020

Axelrod Symposium 2019: Phosphoproteomic Analysis of G-Protein-Coupled Pathways.

Mol Pharmacol 2021 05 28;99(5):383-391. Epub 2020 Feb 28.

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom

By limiting unrestricted activation of intracellular effectors, compartmentalized signaling of cyclic nucleotides confers specificity to extracellular stimuli and is critical for the development and health of cells and organisms. Dissecting the molecular mechanisms that allow local control of cyclic nucleotide signaling is essential for our understanding of physiology and pathophysiology, but mapping the dynamics and regulation of compartmentalized signaling is a challenge. In this minireview we summarize advanced imaging and proteomics techniques that have been successfully used to probe compartmentalized cAMP signaling in eukaryotic cells. Read More

View Article and Full-Text PDF

Cyclin-Dependent Kinase 5-Dependent BAG3 Degradation Modulates Synaptic Protein Turnover.

Biol Psychiatry 2020 04 21;87(8):756-769. Epub 2019 Nov 21.

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, China. Electronic address:

Background: Synaptic protein dyshomeostasis and functional loss is an early invariant feature of Alzheimer's disease (AD), yet the unifying etiological pathway remains largely unknown. Knowing that cyclin-dependent kinase 5 (CDK5) plays critical roles in synaptic formation and degeneration, its phosphorylation targets were reexamined in search of candidates with direct global impacts on synaptic protein dynamics, and the associated regulatory network was also analyzed.

Methods: Quantitative phosphoproteomics and bioinformatics analyses were performed to identify top-ranked candidates. Read More

View Article and Full-Text PDF

Protein synthesis increases with photosynthesis via the stimulation of translation initiation.

Plant Sci 2020 Feb 29;291:110352. Epub 2019 Nov 29.

Plateforme d'Analyse de Protéomique Paris Sud-Ouest (PAPPSO), GQE Le Moulon, INRA, Univ. Paris-Sud, CNRS, AgroParisTech, Université Paris-Saclay, Ferme du Moulon, 91190, Gif-sur-Yvette, France.

Leaf protein synthesis is an essential process at the heart of plant nitrogen (N) homeostasis and turnover that preferentially takes place in the light, that is, when N and CO fixation occur. The carbon allocation to protein synthesis in illuminated leaves generally accounts for ca. 1 % of net photosynthesis. Read More

View Article and Full-Text PDF
February 2020

Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast.

Front Cell Dev Biol 2019 17;7:338. Epub 2019 Dec 17.

Molecular Cell Biology, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany.

The coordination of metabolism and growth with cell division is crucial for proliferation. While it has long been known that cell metabolism regulates the cell division cycle, it is becoming increasingly clear that the cell division cycle also regulates metabolism. In budding yeast, we previously showed that over half of all measured metabolites change concentration through the cell cycle indicating that metabolic fluxes are extensively regulated during cell cycle progression. Read More

View Article and Full-Text PDF
December 2019

Changes in Proteome and Protein Phosphorylation Reveal the Protective Roles of Exogenous Nitrogen in Alleviating Cadmium Toxicity in Poplar Plants.

Int J Mol Sci 2019 Dec 31;21(1). Epub 2019 Dec 31.

College of Forestry, Sichuan Agricultural University, Chengdu 611130, China.

Phytoremediation soil polluted by cadmium has drawn worldwide attention. However, how to improve the efficiency of plant remediation of cadmium contaminated soil remains unknown. Previous studies showed that nitrogen (N) significantly enhances cadmium uptake and accumulation in poplar plants. Read More

View Article and Full-Text PDF
December 2019

R2-P2 rapid-robotic phosphoproteomics enables multidimensional cell signaling studies.

Mol Syst Biol 2019 12;15(12):e9021

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Recent developments in proteomics have enabled signaling studies where > 10,000 phosphosites can be routinely identified and quantified. Yet, current analyses are limited in throughput, reproducibility, and robustness, hampering experiments that involve multiple perturbations, such as those needed to map kinase-substrate relationships, capture pathway crosstalks, and network inference analysis. To address these challenges, we introduce rapid-robotic phosphoproteomics (R2-P2), an end-to-end automated method that uses magnetic particles to process protein extracts to deliver mass spectrometry-ready phosphopeptides. Read More

View Article and Full-Text PDF
December 2019

Phosphoprotein Biosensors for Monitoring Pathological Protein Structural Changes.

Trends Biotechnol 2020 05 26;38(5):519-531. Epub 2019 Dec 26.

Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), Corner College and Cooper Roads, The University of Queensland, Brisbane, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Current biotechnological developments are driving a significant shift towards integrating proteomic analysis with landmark genomic, methylomic, and transcriptomic data to elucidate functional effects. For the majority of proteins, structure and function are closely intertwined. Post-translational protein modifications (e. Read More

View Article and Full-Text PDF

Enzymatic Properties of Recombinant Phospho-Mimetic Photorespiratory Glycolate Oxidases from and .

Plants (Basel) 2019 Dec 24;9(1). Epub 2019 Dec 24.

Institute of Plant Sciences Paris-Saclay, CNRS, Université Paris-Sud, INRA, Université d'Evry, Université Paris-Diderot, Université Paris-Saclay, 91405 Orsay CEDEX, France.

In photosynthetic organisms, the photorespiratory cycle is an essential pathway leading to the recycling of 2-phosphoglycolate, produced by the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase, to 3-phosphoglycerate. Although photorespiration is a widely studied process, its regulation remains poorly understood. In this context, phosphoproteomics studies have detected six phosphorylation sites associated with photorespiratory glycolate oxidases from (GOX1 and GOX2). Read More

View Article and Full-Text PDF
December 2019

Sequential phosphoproteomics and N-glycoproteomics of plasma-derived extracellular vesicles.

Nat Protoc 2020 01 20;15(1):161-180. Epub 2019 Dec 20.

Department of Chemistry, Purdue University, West Lafayette, IN, USA.

Extracellular vesicles (EVs) are increasingly being recognized as important vehicles for intercellular communication and as promising sources for biomarker discovery. Because the state of protein post-translational modifications (PTMs) such as phosphorylation and glycosylation can be a key determinant of cellular physiology, comprehensive characterization of protein PTMs in EVs can be particularly valuable for early-stage diagnostics and monitoring of disease status. However, the analysis of PTMs in EVs has been complicated by limited amounts of purified EVs, low-abundance PTM proteins, and interference from proteins and metabolites in biofluids. Read More

View Article and Full-Text PDF
January 2020

Analog-sensitive cell line identifies cellular substrates of CDK9.

Oncotarget 2019 Dec 10;10(65):6934-6943. Epub 2019 Dec 10.

Department of Molecular Epigenetics, Helmholtz Center Munich and Center for Integrated Protein Science Munich (CIPSM), Germany.

Transcriptional cyclin-dependent kinases regulate all phases of transcription. Cyclin-dependent kinase 9 (CDK9) has been implicated in the regulation of promoter-proximal pausing of RNA polymerase II and more recently in transcription termination. Study of the substrates of CDK9 has mostly been limited to approaches that lack a quantitative assessment of CDK9 activity. Read More

View Article and Full-Text PDF
December 2019

Phosphoproteomic Approaches to Discover Novel Substrates of Mycobacterial Ser/Thr Protein Kinases.

Mol Cell Proteomics 2020 02 15;19(2):233-244. Epub 2019 Dec 15.

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates. Electronic address:

Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive. Read More

View Article and Full-Text PDF
February 2020

Metabolic rewiring of the hypertensive kidney.

Sci Signal 2019 12 10;12(611). Epub 2019 Dec 10.

Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92122, USA.

Hypertension is a persistent epidemic across the developed world that is closely associated with kidney disease. Here, we applied a metabolomic, phosphoproteomic, and proteomic strategy to analyze the effect of hypertensive insults on kidneys. Our data revealed the metabolic aspects of hypertension-induced glomerular sclerosis, including lipid breakdown at early disease stages and activation of anaplerotic pathways to regenerate energy equivalents to counter stress. Read More

View Article and Full-Text PDF
December 2019

Integrative proteomics and phosphoproteomics in pulmonary arterial hypertension.

Sci Rep 2019 12 9;9(1):18623. Epub 2019 Dec 9.

Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.

Pulmonary arterial endothelial cells (PAEC) are mechanistically linked to origins of pulmonary arterial hypertension (PAH). Here, global proteomics and phosphoproteomics of PAEC from PAH (n = 4) and healthy lungs (n = 5) were performed using LC-MS/MS to confirm known pathways and identify new areas of investigation in PAH. Among PAH and control cells, 170 proteins and 240 phosphopeptides were differentially expressed; of these, 45 proteins and 18 phosphopeptides were located in the mitochondria. Read More

View Article and Full-Text PDF
December 2019

MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia.

Sci Rep 2019 12 9;9(1):18630. Epub 2019 Dec 9.

H12O-CNIO Haematological Malignancies Clinical Research Unit, Hospital 12 de Octubre - Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.

FMS-like tyrosine kinase 3 (FLT3) is a key driver of acute myeloid leukemia (AML). Several tyrosine kinase inhibitors (TKIs) targeting FLT3 have been evaluated clinically, but their effects are limited when used in monotherapy due to the emergence of drug-resistance. Thus, a better understanding of drug-resistance pathways could be a good strategy to explore and evaluate new combinational therapies for AML. Read More

View Article and Full-Text PDF
December 2019

The Syk Kinase Promotes Mammary Epithelial Integrity and Inhibits Breast Cancer Invasion by Stabilizing the E-Cadherin/Catenin Complex.

Cancers (Basel) 2019 Dec 7;11(12). Epub 2019 Dec 7.

IRCM, Inserm, CNRS, Univ Montpellier, ICM, 208 Rue des Apothicaires, 34298 Montpellier, France.

While first discovered in immunoreceptor signaling, the Syk protein kinase behaves as a tumor and metastasis suppressor in epithelial cells. Its reduced expression in breast and other carcinomas is correlated with decreased survival and increased metastasis risk, but its action mechanism remains largely unknown. Using phosphoproteomics we found that Syk phosphorylated E-cadherin and α-, β-, and p120-catenins on multiple tyrosine residues that concentrate at intercellular junctions. Read More

View Article and Full-Text PDF
December 2019

The mechanism of cancer drug addiction in ALK-positive T-Cell lymphoma.

Oncogene 2020 03 5;39(10):2103-2117. Epub 2019 Dec 5.

Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.

Rational new strategies are needed to treat tumors resistant to kinase inhibitors. Mechanistic studies of resistance provide fertile ground for development of new approaches. Cancer drug addiction is a paradoxical resistance phenomenon, well-described in MEK-ERK-driven solid tumors, in which drug-target overexpression promotes resistance but a toxic overdose of signaling if the inhibitor is withdrawn. Read More

View Article and Full-Text PDF

Scaffold protein GhMORG1 enhances the resistance of cotton to Fusarium oxysporum by facilitating the MKK6-MPK4 cascade.

Plant Biotechnol J 2020 06 20;18(6):1421-1433. Epub 2019 Dec 20.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, China.

In eukaryotes, MAPK scaffold proteins are crucial for regulating the function of MAPK cascades. However, only a few MAPK scaffold proteins have been reported in plants, and the molecular mechanism through which scaffold proteins regulate the function of the MAPK cascade remains poorly understood. Here, we identified GhMORG1, a GhMKK6-GhMPK4 cascade scaffold protein that positively regulates the resistance of cotton to Fusarium oxysporum. Read More

View Article and Full-Text PDF

Comparison of Statistical Tests and Power Analysis for Phosphoproteomics Data.

J Proteome Res 2020 02 26;19(2):572-582. Epub 2019 Dec 26.

Department of Mathematical Sciences and Program of Bioinformatics and Computational Biology and Program of Data Science , Worcester Polytechnic Institute (WPI) , 100 Institute Road , Worcester , Massachusetts 01609 , United States.

Advances in protein tagging and mass spectrometry have enabled generation of large quantitative proteome and phosphoproteome data sets, for identifying differentially expressed targets in case-control studies. The power study of statistical tests is critical for designing strategies for effective target identification and control of experimental cost. Here, we develop a simulation framework to generate realistic phospho-peptide data with known changes between cases and controls. Read More

View Article and Full-Text PDF
February 2020

Colorectal Cancer Growth Retardation through Induction of Apoptosis, Using an Optimized Synergistic Cocktail of Axitinib, Erlotinib, and Dasatinib.

Cancers (Basel) 2019 Nov 27;11(12). Epub 2019 Nov 27.

Molecular Pharmacology Group, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland.

Patients with advanced colorectal cancer (CRC) still depend on chemotherapy regimens that are associated with significant limitations, including resistance and toxicity. The contribution of tyrosine kinase inhibitors (TKIs) to the prolongation of survival in these patients is limited, hampering clinical implementation. It is suggested that an optimal combination of appropriate TKIs can outperform treatment strategies that contain chemotherapy. Read More

View Article and Full-Text PDF
November 2019

Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes.

Int J Mol Sci 2019 Nov 27;20(23). Epub 2019 Nov 27.

Biochemistry and Molecular Genetics Service, Hospital Clínic Universitari, IDIBAPS, CIBERehd, 08036 Barcelona, Spain.

Cerium oxide nanoparticles (CeONPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whether CeONPs can prevent or attenuate oxidant injury in the hepatic human cell line HepG2 and to investigate the mechanisms involved in this phenomenon. The effect of CeONPs on cell viability and ROS scavenging was determined, the differential expression of pro-inflammatory and oxidative stress-related genes was analyzed, and a proteomic analysis was performed to assess the impact of CeONPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. Read More

View Article and Full-Text PDF
November 2019

Global targeting of functional tyrosines using sulfur-triazole exchange chemistry.

Nat Chem Biol 2020 02 25;16(2):150-159. Epub 2019 Nov 25.

Department of Chemistry, University of Virginia, Charlottesville, VA, USA.

Covalent probes serve as valuable tools for global investigation of protein function and ligand binding capacity. Despite efforts to expand coverage of residues available for chemical proteomics (e.g. Read More

View Article and Full-Text PDF
February 2020

Goals and Challenges in Bacterial Phosphoproteomics.

Int J Mol Sci 2019 Nov 13;20(22). Epub 2019 Nov 13.

Área de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain.

Reversible protein phosphorylation at serine, threonine and tyrosine is a well-known dynamic post-translational modification with stunning regulatory and signalling functions in eukaryotes. Shotgun phosphoproteomic analyses revealed that this post-translational modification is dramatically lower in bacteria than in eukaryotes. However, Ser/Thr/Tyr phosphorylation is present in all analysed bacteria (24 eubacteria and 1 archaea). Read More

View Article and Full-Text PDF
November 2019

Phosphoproteomics Enables Molecular Subtyping and Nomination of Kinase Candidates for Individual Patients of Diffuse-Type Gastric Cancer.

iScience 2019 Dec 6;22:44-57. Epub 2019 Nov 6.

State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China. Electronic address:

The diffuse-type gastric cancer (DGC) constitutes a subgroup of gastric cancer with poor prognosis and no effective molecular therapies. Here, we report a phosphoproteomic landscape of DGC derived from 83 tumors together with their nearby tissues. Based on phosphorylation, DGC could be classified into three molecular subtypes with distinct overall survival (OS) and chemosensitivity. Read More

View Article and Full-Text PDF
December 2019

Proteomics of Rice- Interaction: What Have We Learned So Far?

Front Plant Sci 2019 29;10:1383. Epub 2019 Oct 29.

Department of Plant Bioscience, Pusan National University, Miryang, South Korea.

Rice blast disease, caused by , is one of the major constraints to rice production, which feeds half of the world's population. Proteomic technologies have been used as effective tools in plant-pathogen interactions to study the biological pathways involved in pathogen infection, plant response, and disease progression. Advancements in mass spectrometry (MS) and apoplastic and plasma membrane protein isolation methods facilitated the identification and quantification of subcellular proteomes during plant-pathogen interaction. Read More

View Article and Full-Text PDF
October 2019