Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative phosphoproteomic analysis of TCR signaling

ABSTRACT: To define the physiological properties of TCR signaling, We investigated the global dynamic view of TCR-dependent phosphorylation with the use of thymocytes stimulated with antibodies to CD3 to mimic TCR activation

INSTRUMENT(S): QSTAR

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, T Cell

SUBMITTER: Atsushi Hatano

LAB HEAD: Keiichi I. Nakayama

PROVIDER: PXD000969 | Pride | 2022-02-22

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20131026_thymocyte_CD3_whole_01.mgf	Mgf
	20131026_thymocyte_CD3_whole_01.pride.mgf.gz	Mgf
	20131026_thymocyte_CD3_whole_02.mgf	Mgf
	20131026_thymocyte_CD3_whole_02.pride.mgf.gz	Mgf
	20131031_thymocyte_CD3_fr1-2.mgf	Mgf

Items per page:

1 - 5 of 51

Publications

Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling.

Hatano Atsushi A Matsumoto Masaki M Nakayama Keiichi I KI

Genes to cells : devoted to molecular & cellular mechanisms 20160907 10

A key issue in the study of signal transduction is how multiple signaling pathways are systematically integrated into the cell. We have now performed multiple phosphoproteomics analyses focused on the dynamics of the T-cell receptor (TCR) signaling network and its subsystem mediated by the Ca<sup>2+</sup> signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca<sup>2+</sup> signaling showed unexpected phosphoryl ...[more]

PMID: 27600695

Similar Datasets

Phosphoproteomic analysis of TCR signaling with inhibitors

Project description:MAPK-Erk and calcium-Calcineurin pathways are major signaling pathways activated during TCR signal transduction. We investigated the effect of these signaling pathway with the use of selective inhibitors of Mek and calcineurin.

2022-02-22 | PXD000972 | Pride

Phosphoproteomic analysis of calcium signaling

Project description:Calcium signaling plays a pivotal role in t cell activation through activation of kinases and phosphatases, but comprehensive analysis to overview calcium-induced phosphorylation has never been performed. To investigate Ca2+-mediated phosphorylation globally, we next undertook a phosphoproteomic analysis of calcium signaling, especially focused on the Ca2+-dependent phosphatase, calcineurin. Normal mouse thymocytes were stimulated in 4 different conditions; 1). DMSO, 2). CsA, 3). IOM, or 4). CsA and IOM, and compared their phosphorylation status.

2022-02-22 | PXD000973 | Pride

Noncanonical pathway for regulation of CCL2 expression by an mTORC1-FOXK1 axis promotes recruitment of tumor-associated macrophages

Project description:C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)–κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase that is activated in various tumor cell types. We have now identified a noncanonical pathway for regulation of CCL2 production that is mediated by mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1, with dephosphorylation of FOXK1 in response to mTORC1 activation resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB, and that CCL2 produced by this pathway contributes to tumor progression. Specific inhibition of FOXK1 may thus be a potential therapeutic strategy for cancer.

2017-11-30 | PXD007996 | Pride

Comparative analysis of the human and mouse placental transcriptome and proteome

Project description:An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities but there have been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies. Over 7,000 orthologs were detected with 70% co-expressed and over 80% of genes known to cause placental phenotypes in mouse were co-expressed. These genes form a tight protein-protein interaction network with novel candidate genes likely to be important in placental structure and/or function. The entire data is available as a web-accessible database to guide the informed development of mouse models to study human disease This experiment is now fully represented in NCBI Peptidome database with accession PSE115; http://www.ncbi.nlm.nih.gov/peptidome/search/index.shtml?acc=PSE115 Microdissection of human villous trees and mouse placental labyrinth. Tissues were split for microarray and protein analysis. For protein analysis samples were first fractionated by differential sucrose gradients into mitochrondria, cytosol, microsomes and nuclei. Mitochrondira and neuclei were each extracted by two different methods for soluble and insoluble material. Each subcellular fraction for each tissue was analysed in quintuplet by 9 step 2 dimensional LC/MSMS. This generated a total of 270 mzXML files for each tissue.

2009-06-29 | E-GEOD-13299 | biostudies-arrayexpress

Effects on the transcriptome of adult mouse pancreas (principally acinar cells) by the inactivation of the Ptf1a gene in vivo

Project description:RNA-seq analysis documented mRNA changes in total pancreatic RNA preparations 14 days after Ptf1a inactivation. pancreas mRNA profiles of Tamoxifen treated adult control mice [Ptf1a(CreER/+)] and Ptf1a conditional knockout mice [Ptf1a(CreER/fl)] were generated by deep sequencing using an Illumina Hiseq 2500.

2015-07-22 | E-GEOD-70542 | biostudies-arrayexpress

Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways

Project description:Numerous observations indicate that red blood cells (RBCs) affect T-cell activation and proliferation. We have studied effects of packed RBCs (PRBCs) on T-cell-receptor (TCR) signaling and the molecular mechanisms whereby (P)RBCs modulate T-cell activation. In line with previous reports, PRBCs attenuated the expression of T-cell activation markers CD25 and CD69 upon co-stimulation via CD3/CD28. In addition, T-cell proliferation and cytokine expression were markedly reduced when T-cells were stimulated in presence of PRBCs. Inhibitory activity of PRBCs required direct cell-cell contact and intact PRBCs. The production of activation-induced cellular reactive oxygen species (ROS), which act as second messengers in T-cells, was completely abrogated to levels of unstimulated T-cells in presence of PRBCs. Phosphorylation of the TCR-related zeta-chain and thus proximal TCR signal transduction was unaffected by PRBCs, ruling out mechanisms based on secreted factors and steric interaction restrictions. Only downstream signaling events requiring ROS for full functionality were affected, confirmed by an untargeted mass spectrometry-based phosphoproteomics approach. PRBCs inhibited T-cell activation more efficiently than did treatment with 1 mM of the anti-oxidant N-acetyl cysteine. Taken together, our data suggest that inflammation-related radical reactions are modulated by PRBCs. These immunomodulating effects might be responsible for clinical observations associated with transfusion of PRBCs.

2021-06-01 | PXD023144 | Pride

Integrated approaches reveal determinants of genome-wide binding and function of the transcription factor Pho4

Project description:Binding of transcription factors to DNA is a key regulatory step in the control of gene expression. DNA sequences with high affinity for transcription factors occur more frequently in the genome than instances of genes bound or regulated by these factors. Although several mechanisms have been identified that influence the specificity of transcriptional regulation, it is not known if these can explain the observed genome-wide pattern of binding or regulation for a given transcription factor. We used genome-wide approaches to study how trans influences shape the binding and regulatory landscape of Pho4, a budding yeast transcription factor that activates gene expression in response to phosphate limitation. We find that nucleosomes significantly restrict the sites to which Pho4 binds. At nucleosome-depleted sites, competition between Pho4 and another transcription factor, Cbf1, determines Pho4 occupancy, raising the threshold for transcriptional activation by Pho4 in phosphate replete conditions and preventing Pho4 activation of genes outside the phosphate regulon during phosphate starvation. Pho4 binding is not sufficient for transcriptional activation - a cooperative interaction between the transcription factor Pho2 and Pho4 occurs specifically at genes that are activated. Combining these experimental observations, we are able to globally predict Pho4 binding and its functionality. Our study provides insights into the mechanisms of global control by sequence-specific transcription factors. ChIP-Seq experiments of Pho4, Pho2 and Cbf1 samples and paired-end nucleosome sequencing in no Pi conditions.

2011-09-27 | E-GEOD-29506 | biostudies-arrayexpress

RNA-seq of wild-type and Utx- or Hnf1a-deficient mouse pancreas

Project description:HNF1A and UTX are putative tumor suppressors in pancreatic cancer. In this study, we have combined mouse genetics, transcriptomics and genome binding studies to link HNF1A and UTX in a molecular mechanism that suppresses pancreatic cancer. In this session, we have determined the transcriptome of HNF1A and UTX in the exocrine pancreas. We show that HNF1A recruits UTX to its genomic targets in pancreatic acinar cells, which results in remodeling of the chromatin landscape and activation of a broad transcriptional program of differentiated acinar cells, which in turn indirectly suppresses tumor suppressor pathways.

2019-12-20 | E-MTAB-7945 | biostudies-arrayexpress

HDX-MS Analysis of Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2

Project description:Activation of the extracellular signal regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states, named “L” and “R”, where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.

2024-03-20 | PXD048311 | Pride

mouse liver microsomes phosphorylation with LC-MS/MS

Project description:The microsomes are re-formed vesicle-like artifacts, not ordinarily present in living cells, from pieces of the endoplasmic reticulum (ER), plasma membrane, mitochondria, and Golgi apparatus of broken eukaryotic cells. Typically, microsomes are separated by differential centrifuged from homogenized of cell or tissue. Based on enrichment of ER fractions, prepared microsomes mainly show a large of metabolic activity following high amount of metabolic enzyme, as cytochrome P450 (CYP). CYPs are important components of xenobiotic-metabolizing monooxygenase accounting for an approximate 75% of biotransformation of clinically relevant drugs. Hepatic CYP are ER-anchored hemoproteins involved in the metabolism of numerous endo- and xenobiotics including drugs, steroids, and carcinogens. The CYPs catalytic activity is subject to regulation via phosphorylation. In several previous studies, 8 CYP phosphorylation sites had been discovered in human. Protein kinase A (PKA) and protein kinase C (PKC) were identified as a major catalyst for the phosphorylation of CYPs in 2003. The phosphorylation of CYPs process to their ubiquitination undergoing ubiquitin-dependent 26S proteosomal degradation.

2017-04-04 | PXD003043 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data