Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination

Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/ . Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (“adherens junction,” “tight junction,” and “focal adhesion”) and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.

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The elusive phosphotyrosine: pinning down a rare species. Focus on “Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination”

AJP Cell Physiology ◽

10.1152/ajpcell.00363.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. C16-C17

Author(s):

Carolyn M. Ecelbarger

Keyword(s):

Cell Polarity ◽

Rare Species ◽

Large Scale ◽

Collecting Duct ◽

Proteomic Profiling ◽

Duct Epithelium ◽

Polarity Determination ◽

Renal Collecting Duct ◽

Collecting Duct Epithelium

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Protein-protein-interaction Network Organization of the Hypusine Modification System

Molecular & Cellular Proteomics ◽

10.1074/mcp.m112.019059 ◽

2012 ◽

Vol 11 (11) ◽

pp. 1289-1305 ◽

Cited By ~ 12

Author(s):

Henning Sievert ◽

Simone Venz ◽

Oscar Platas-Barradas ◽

Vishnu M. Dhople ◽

Martin Schaletzky ◽

...

Keyword(s):

Protein Interaction ◽

Large Scale ◽

Affinity Purification ◽

Interaction Network ◽

Initiation Factor ◽

Post Translational Modification ◽

Comprehensive Overview ◽

Data Set ◽

Modification System ◽

Protein Protein Interaction

Hypusine modification of eukaryotic initiation factor 5A (eIF-5A) represents a unique and highly specific post-translational modification with regulatory functions in cancer, diabetes, and infectious diseases. However, the specific cellular pathways that are influenced by the hypusine modification remain largely unknown. To globally characterize eIF-5A and hypusine-dependent pathways, we used an approach that combines large-scale bioreactor cell culture with tandem affinity purification and mass spectrometry: “bioreactor-TAP-MS/MS.” By applying this approach systematically to all four components of the hypusine modification system (eIF-5A1, eIF-5A2, DHS, and DOHH), we identified 248 interacting proteins as components of the cellular hypusine network, with diverse functions including regulation of translation, mRNA processing, DNA replication, and cell cycle regulation. Network analysis of this data set enabled us to provide a comprehensive overview of the protein-protein interaction landscape of the hypusine modification system. In addition, we validated the interaction of eIF-5A with some of the newly identified associated proteins in more detail. Our analysis has revealed numerous novel interactions, and thus provides a valuable resource for understanding how this crucial homeostatic signaling pathway affects different cellular functions.

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Global and hemispheric climate variations affecting the Southern Ocean

Antarctic Science ◽

10.1017/s0954102004002226 ◽

2004 ◽

Vol 16 (4) ◽

pp. 401-413 ◽

Cited By ~ 69

Author(s):

IAN SIMMONDS ◽

JOHN C. KING

Keyword(s):

Southern Ocean ◽

Fresh Water ◽

Large Scale ◽

Mechanical Energy ◽

Large Fraction ◽

World Ocean ◽

Southern Annular Mode ◽

Reanalysis Data ◽

Data Set ◽

The Pacific

The hemispheric and regional atmospheric circulation influences the Southern Ocean in many and profound ways, including intense air-sea fluxes of momentum, energy, fresh water and dissolved gases. The Southern Ocean ventilates a large fraction of the world ocean and hence these influences are spread globally. We use the NCEP-2 reanalysis data set to diagnose aspects of the large-scale atmospheric structure and variability and explore how these impact on the Southern Ocean. We discuss how the ‘Southern Annular Mode’ and the ‘Pacific-South American’ pattern influence the Southern Ocean, particularly in the eastern Pacific. We review the importance of atmospheric eddies in Southern Ocean climate, and the role they play in the transport of mechanical energy into the ocean. The fluxes of fresh water across the air-sea boundary influence strongly the processes of water mass formation. It is shown that climatological precipitation exceeds evaporation over most of the Southern Ocean. When averaged over the ocean from 50°S to the Antarctic coast the annual mean excess is 0.80 mm day−1. The magnitude of the flux displays only a small measure of seasonality, and its largest value of 0.92 mm day−1 occurs in summer.

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iProMix: A decomposition model for studying the function of ACE2 based on bulk proteogenomic data for coronavirus pathogenesis

10.1101/2021.05.07.441534 ◽

2021 ◽

Author(s):

Xiaoyu Song ◽

Jiayi Ji ◽

Pei Wang

Keyword(s):

Epithelial Cells ◽

Large Scale ◽

Interferon Α ◽

Proteomic Profiling ◽

Cell Type ◽

Large Power ◽

Association Analyses ◽

Proteomic Data ◽

Cell Type Composition ◽

Type Composition

Both SARS-CoV and SARS-CoV-2 use ACE2 receptors to enter epithelial cells in lung and many other tissues to cause human diseases. Genes and pathways that regulate ACE2 may facilitate/inhibit viral entry and replication, and genes and pathways that are controlled by ACE2 may be perturbed during infection, both affecting disease severity and outcomes. It is critical to understand how genes and pathways are associated with ACE2 in epithelial cells by leveraging proteomic data, but an accurate large-scale proteomic profiling at cellular resolution is not feasible at current stage. Therefore, we propose iProMix, a novel framework that decomposes bulk tissue proteomic data to identify epithelial cell component specific associations between ACE2 and other proteins. Unlike existing decomposition based association analyses, iProMix allows both predictors and outcomes to be impacted by cell type composition of the tissue and accounts for the impacts of decomposition variations and errors on hypothesis tests. It also builds in the functions to improve cell type estimation if estimates from existing literature are unsatisfactory. Simulations demonstrated that iProMix has well-controlled false discovery rate and large power in non-asymptotic settings with both correctly and mis-specified cell-type composition. We applied iProMix to the 110 adjacent normal tissue samples of patients with lung adenocarcinoma from Clinical Proteomic Tumor Analysis Consortium, and identified that interferon α and γ pathways were most significantly associated with ACE2 protein abundances in epithelial cells. Interestingly, the associations were sex-specific that the positive associations were only observed in men, while in women the associations were negative.

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Large‐scale phosphoproteomic profiling of native rat renal collecting duct epithelium: Tyrosine phosphorylation

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.921.11 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

B Zhao ◽

T Pisitkun ◽

J Hoffert ◽

CL Chou ◽

M Knepper

Keyword(s):

Tyrosine Phosphorylation ◽

Large Scale ◽

Collecting Duct ◽

Duct Epithelium ◽

Renal Collecting Duct ◽

Collecting Duct Epithelium

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Faculty Opinions recommendation of Large-scale phosphorylation mapping reveals the extent of tyrosine phosphorylation in Arabidopsis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108705.564804 ◽

2008 ◽

Author(s):

Lieven De Veylder

Keyword(s):

Tyrosine Phosphorylation ◽

Large Scale

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ProGen:Provenance database generator for large-scale data set

Journal of Computer Applications ◽

10.3724/sp.j.1087.2008.02737 ◽

2009 ◽

Vol 28 (11) ◽

pp. 2737-2740

Author(s):

Xiao ZHANG ◽

Shan WANG ◽

Na LIAN

Keyword(s):

Large Scale ◽

Data Set ◽

Large Scale Data ◽

Scale Data

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Integrative Data Analysis from a Unifying Research Synthesis Perspective

10.1093/oso/9780190676001.003.0020 ◽

2018 ◽

Author(s):

Eun-Young Mun ◽

Anne E. Ray

Keyword(s):

Data Analysis ◽

Large Scale ◽

Research Synthesis ◽

Alcohol Intervention ◽

Data Set ◽

Integrative Data Analysis ◽

Level Data ◽

Model Complex ◽

Wide Range ◽

Individual Participant

Integrative data analysis (IDA) is a promising new approach in psychological research and has been well received in the field of alcohol research. This chapter provides a larger unifying research synthesis framework for IDA. Major advantages of IDA of individual participant-level data include better and more flexible ways to examine subgroups, model complex relationships, deal with methodological and clinical heterogeneity, and examine infrequently occurring behaviors. However, between-study heterogeneity in measures, designs, and samples and systematic study-level missing data are significant barriers to IDA and, more broadly, to large-scale research synthesis. Based on the authors’ experience working on the Project INTEGRATE data set, which combined individual participant-level data from 24 independent college brief alcohol intervention studies, it is also recognized that IDA investigations require a wide range of expertise and considerable resources and that some minimum standards for reporting IDA studies may be needed to improve transparency and quality of evidence.

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Financial distress determinants among SMEs: empirical evidence from Sweden

Journal of Economic Studies ◽

10.1108/jes-01-2019-0030 ◽

2020 ◽

Vol 47 (3) ◽

pp. 547-560 ◽

Cited By ~ 1

Author(s):

Darush Yazdanfar ◽

Peter Öhman

Keyword(s):

Financial Crisis ◽

Financial Distress ◽

Large Scale ◽

Global Financial Crisis ◽

Binary Logistic Regression ◽

Data Availability ◽

Cross Sectional ◽

Data Set ◽

Content Type ◽

The Global Financial Crisis

PurposeThe purpose of this study is to empirically investigate determinants of financial distress among small and medium-sized enterprises (SMEs) during the global financial crisis and post-crisis periods.Design/methodology/approachSeveral statistical methods, including multiple binary logistic regression, were used to analyse a longitudinal cross-sectional panel data set of 3,865 Swedish SMEs operating in five industries over the 2008–2015 period.FindingsThe results suggest that financial distress is influenced by macroeconomic conditions (i.e. the global financial crisis) and, in particular, by various firm-specific characteristics (i.e. performance, financial leverage and financial distress in previous year). However, firm size and industry affiliation have no significant relationship with financial distress.Research limitationsDue to data availability, this study is limited to a sample of Swedish SMEs in five industries covering eight years. Further research could examine the generalizability of these findings by investigating other firms operating in other industries and other countries.Originality/valueThis study is the first to examine determinants of financial distress among SMEs operating in Sweden using data from a large-scale longitudinal cross-sectional database.

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