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Phosphoproteomic analysis of TCR signaling with inhibitors

ABSTRACT: 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.

INSTRUMENT(S): QSTAR

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, T Cell

SUBMITTER: Atsushi Hatano

LAB HEAD: Keiichi I. Nakayama

PROVIDER: PXD000972 | Pride | 2022-02-22

REPOSITORIES: Pride

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			Action	DRS
	20130921_thymocyte_iTRAQ_whole.mgf	Mgf
	20130921_thymocyte_iTRAQ_whole.pride.mgf.gz	Mgf
	20130921_thymocyte_iTRAQ_whole_2.mgf	Mgf
	20130921_thymocyte_iTRAQ_whole_2.pride.mgf.gz	Mgf
	20130924_thymocyte_iTRAQ_whole2_1.mgf	Mgf

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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

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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

Quantitative phosphoproteomic analysis of TCR signaling

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2022-02-22 | PXD000969 | 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.

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

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