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Comparative analysis of phosphorylated proteomes between plerocercoid and adult Spirometra mansoni reveal phosphoproteomic proflings of the medical tapeworm

ABSTRACT: Site-specific phosphoproteomics analysis using 4DLabel Free quantitative analysis technology was performed to obtain the primary information about the overall phosphorylation status of the plerocercoid and adult stages. The dataset reported herein provides a valuable resource for future studies on the signaling pathways of Spirometra mansoni.

ORGANISM(S): Spirometra Erinaceieuropaei

SUBMITTER: Xi Zhang

PROVIDER: PXD048134 | iProX | Tue Dec 26 00:00:00 GMT 2023

REPOSITORIES: iProX

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Comparative analysis of phosphorylated proteomes between plerocercoid and adult Spirometra mansoni reveals phosphoproteomic profiles of the medical tapeworm.

Project description:BackgroundPlerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni.MethodsIn this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults.ResultsA total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni.ConclusionsThe dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni.

| S-EPMC11366163 | biostudies-literature

Proteomics and phosphoproteomics reveal immune and detoxification-related functions of cystatin vaccines against adult ticks Haemaphysalis doenitzi ovary

Project description:Proteomics and phosphoproteomics reveal immune and detoxification-related functions of cystatin vaccines against adult ticks Haemaphysalis doenitzi ovary

2024-08-28 | PXD055423 |

Phosphoproteomic Analysis of Breast Cancer-Derived Small Extracellular Vesicles Reveals Disease-Specific Phosphorylated Enzymes.

Project description:Small membrane-derived extracellular vesicles have been proposed as participating in several cancer diseases, including breast cancer (BC). We performed a phosphoproteomic analysis of breast cancer-derived small extracellular vesicles (sEVs) to provide insight into the molecular and cellular regulatory mechanisms important for breast cancer tumor progression and metastasis. We examined three cell line models for breast cancer: MCF10A (non-malignant), MCF7 (estrogen and progesterone receptor-positive, metastatic), and MDA-MB-231 (triple-negative, highly metastatic). To obtain a comprehensive overview of the sEV phosphoproteome derived from each cell line, effective phosphopeptide enrichment techniques IMAC and TiO2, followed by LC-MS/MS, were performed. The phosphoproteome was profiled to a depth of 2003 phosphopeptides, of which 207, 854, and 1335 were identified in MCF10A, MCF7, and MDA-MB-231 cell lines, respectively. Furthermore, 2450 phosphorylation sites were mapped to 855 distinct proteins, covering a wide range of functions. The identified proteins are associated with several diseases, mostly related to cancer. Among the phosphoproteins, we validated four enzymes associated with cancer and present only in sEVs isolated from MCF7 and MDA-MB-231 cell lines: ATP citrate lyase (ACLY), phosphofructokinase-M (PFKM), sirtuin-1 (SIRT1), and sirtuin-6 (SIRT6). With the exception of PFKM, the specific activity of these enzymes was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study demonstrates that sEVs contain functional metabolic enzymes that could be further explored for their potential use in early BC diagnostic and therapeutic applications.

| S-EPMC8962341 | biostudies-literature

Integration of Thermal Proteome Profiling with phosphoproteomic and transcriptomic data via mechanistic network models decodes the molecular response to PARP inhibition

Project description:The deregulation of complex diseases often spans multiple molecular processes. A multimodal functional characterization of these processes can shed light on the disease mechanisms and the effect of drugs. Thermal Proteome Profiling (TPP) is a mass-spectrometry based technique assessing changes in thermal protein stability that can serve as proxies of functional changes of the proteome. These unique insights of TPP can complement those obtained by other omics technologies. Here, we show how TPP can be integrated with phosphoproteomics and transcriptomics in a network-based approach using COSMOS, a framework for causal integration of multi-omics, to provide an integrated view of transcription factors, kinases and proteins with altered thermal stability. This allowed us to recover known mechanistic consequences of PARP inhibition in ovarian cancer cells on cell cycle and DNA damage response in detail and to uncover new insights into drug response mechanisms related to interferon and hippo signaling. We found that TPP complements the other omics data and allowed us to obtain a network model with higher coverage of the main underlying mechanisms. These results illustrate the added value of TPP, and more generally the power of network models to integrate the information provided by different omics technologies. We anticipate that this strategy can be used to broadly integrate functional proteomics with other omics to study complex molecular processes.

2024-04-10 | GSE243208 | GEO

Comparative phosphoproteomic analysis of neonatal and adult murine brain.

Project description:Developmental processes are governed by diverse regulatory mechanisms including a suite of signaling pathways employing reversible phosphorylation. With the advent of large-scale phosphoproteomics, it is now possible to identify thousands of phosphorylation sites from tissues at distinct developmental stages. We describe here the identification of over 6000 nonredundant phosphorylation sites from neonatal murine brain. When compared to nearly three times the number of phosphorylation sites identified from 3-week-old murine brain, remarkably one-third of the neonatal sites were unique. This fraction only dropped to one-quarter when allowing the site to stray plus or minus 15 residues. This provides evidence for considerable change in the profiles of developmentally regulated phosphoproteomes. Using quantitative MS we characterized a novel phosphorylation site (Ser265) identified uniquely in the neonatal brain on doublecortin (Dcx), a protein essential for proper mammalian brain development. While the relative levels of Dcx and phospho-Ser265 Dcx between embryonic and neonatal brain were similar, their levels fell precipitously by postnatal day 21, as did phospho-Ser297, a site required for proper neuronal migration. Both sites lie near the microtubule-binding domain and may provide functionally similar regulation via different kinases.

| S-EPMC3816108 | biostudies-literature

Resource for Genetic Epidemiology Research in Adult Health and Aging (“GERA”)

Project description:Resource for Genetic Epidemiology Research in Adult Health and Aging (“GERA”)

| PRJNA226739 | ENA

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors

Project description:This is a first-in-human, open-label, multi-center, Phase 1/2, dose-escalation study with expansion cohorts to evaluate NM21-1480 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary evidence of the clinical activity in adult patients with selected advanced solid tumors.

| 2343359 | ecrin-mdr-crc

High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development

Project description:Primary human hepatocytes are widely used to evaluate liver toxicity of drugs, but they are scarce and demanding to culture. Stem cell-derived hepatocytes are increasingly discussed as alternatives. To obtain a better appreciation of the molecular processes during the differentiation of induced pluripotent stem cells into hepatocytes, we employ a quantitative proteomic approach to follow the expression of 9,000 proteins, 12,000 phosphorylation sites, and 800 acetylation sites over time. The analysis reveals stage-specific markers, a major molecular switch between hepatic endoderm versus immature hepatocyte-like cells impacting e.g. metabolism, the cell cycle, kinase activity, and the expression of drug transporters. Comparing the proteomes of 2D and 3D-derived hepatocytes to fetal and adult liver, indicate a fetal-like status of the in vitro models and lower expression of important ADME/Tox proteins. The collective data enable constructing a molecular roadmap of hepatocyte development that serve as a valuable resource for future research.

2022-04-01 | PXD027439 | Pride

The Fly Cell Atlas: single-cell transcriptomes of the entire adult Drosophila - 10x dataset

Project description:Single-cell technologies have ushered in a new era for Drosophila research, allowing researchers to obtain transcriptomes for all stable cell types and dynamic cell states. Here we present the first release of the adult Fly Cell Atlas (FCA), which includes 580k cells from 15 individually dissected sexed tissues, as well as from the entire head and body. We annotated more than 250 distinct cell types across all tissues. Few cell types were uniquely detected in the entire head and body samples, suggesting high cell-type saturation. We provide an in-depth analysis of gene signatures and transcription factor combinations, as well as sexual dimorphism, across the whole animal. Finally, we studied cell type lineages that are shared between tissues, such as blood cells and muscle cells, allowing the retrieval of rare cell types and tissue- specific subtypes. This atlas provides a valuable resource for the entire Drosophila community as a reference to study genetic perturbations and disease models at single-cell resolution.

2021-07-01 | E-MTAB-10519 | biostudies-arrayexpress

A phosphoproteomic and transcriptomic analysis of carnosine’s action on signaling in glioblastoma

Project description:Previous studies demonstrated that carnosine affects signaling molecules of different pathways in a number of experimental models. However, the primary targets of carnosine are still unknown and its effect on complex signal transduction has not been revealed. This is especially the case for pathways that could be responsible for the anti-neoplastic effect of the dipeptide. Therefore, we performed a phosphoprotein antibody array and RNA-seq experiments with U87 glioblastoma cells treated with 50 mM carnosine for 24h, in order to obtain a precise and coherent picture of carnosine’s influence on signal transduction in single tumor cells.

2019-05-01 | GSE110767 | GEO

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