Mus musculus
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ABSTRACT:
PROVIDER: PRJNA196152 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ras/cAMP signal transduction, perturbations
| PRJNA92621 | ENA
Project description:It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome. First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells. We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level TCR stimulus. Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments as being differentially regulated by N-ras (Dntt, Slc9a6, Chst1, and Lars2). Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types. Since we were interested primarily in genes that were differentially regulated by N-ras following a low-level TCR stimulus, our microarray data comparison was between data from TCR-stimulated, WT CD4+ T-cells and from TCR-stimulated, N-ras KO CD4+ T-cells. Genes that were differentially regulated in the comparison between stimulated N-ras KO CD4+ T-cells and unstimulated N-ras KO CD4+ T-cells, as well as those genes that were differentially regulated in the comparison between stimulated WT CD4+ T-cells and unstimulated WT CD4+ T-cells were excluded from this analysis. To determine if N-ras and H-ras regulate different sets of genes in thymocytes, a comparison was made between the set of genes that were differentially regulated by N-ras in the [WT] vs. [N-ras KO] comparison and the set of genes that were differentially regulated by H-ras in the [WT] vs. [H-ras KO] comparison. RNA was extracted from CD4+ T cell splenocytes isolated from 6-20 week old N-Ras KO and WT mice following growth in T cell growth media either with or without 1 microgram/milliliter ant-CD3 and anti-CD28 antibodies. RNA was extracted from thymocytes isolated directly from 6-20 week old N-Ras KO, H-Ras KO and WT mice.
2013-04-04 | E-GEOD-45739 | biostudies-arrayexpress
Project description:It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome. First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells. We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level TCR stimulus. Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments as being differentially regulated by N-ras (Dntt, Slc9a6, Chst1, and Lars2). Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types. Since we were interested primarily in genes that were differentially regulated by N-ras following a low-level TCR stimulus, our microarray data comparison was between data from TCR-stimulated, WT CD4+ T-cells and from TCR-stimulated, N-ras KO CD4+ T-cells. Genes that were differentially regulated in the comparison between stimulated N-ras KO CD4+ T-cells and unstimulated N-ras KO CD4+ T-cells, as well as those genes that were differentially regulated in the comparison between stimulated WT CD4+ T-cells and unstimulated WT CD4+ T-cells were excluded from this analysis. To determine if N-ras and H-ras regulate different sets of genes in thymocytes, a comparison was made between the set of genes that were differentially regulated by N-ras in the [WT] vs. [N-ras KO] comparison and the set of genes that were differentially regulated by H-ras in the [WT] vs. [H-ras KO] comparison.
2013-04-04 | GSE45739 | GEO
Project description:It is known that ubiquitination is important for T cell receptor (TCR) signaling during T cell activation but the breadth of ubiquitination events triggered during TCR signaling is not completely understood. This dataset utilizes di-glycine remnant profiling combined with mass spectrometry to identify a global landscape of ubiquitination events downstream of the TCR and to quantify changes ubiquitin abundance in response to TCR stimulation. Additionally, whole cell proteomics data were generated to measure protein abundances during TCR stimulation. Mouse primary T cells were isolated, proliferated and either remained resting or stimulated with CD3/CD28 to activate downstream signaling through the TCR and co-stimulatory pathways. Di-glycine remnant profiling and whole cell proteomics was performed on rested cells and cells that had undergone CD3/CD28 TCR stimulation for 4 hours. These data were analyzed to identify the ubiquitination events during TCR activation and to quantify the change in peptide-based ubiquitin abundance and total protein abundance over the course of the 4 hour TCR stimulation. Integration of di-glycine and whole cell proteomics was used to generate protein-specific predictions of whether ubiquitination events downstream of TCR signaling lead to a decrease in associated protein abundance. The analysis of these data suggests that T cell activation leads to an increase in ubiquitination that is not associated with proteasomal or lysosomal degradation.
2019-05-09 | PXD012831 | Pride
Project description:Transmembrane adaptors on T cells play crucial roles in TCR signal transduction. Although the TCR-LAT signal-transduction axis occupies a central place in T cell activation, it does not work in isolation and is tuned by other T-cell surface receptors among which stand the CD5 and CD6 receptors. Here we assessed the extent of transcriptional changes that initiated by TCR-CD28 pathways in the absence of CD5, of CD6, of both CD5 and CD6, or of LAT by RNA-seq analysis.
2020-09-29 | GSE148721 | GEO
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
Project description:Signal transduction pathways guided by cellular receptors commonly exhibit low-level constitutive signaling in a continuous, ligand-independent manner. The dynamic equilibrium of positive and negative regulators establishes such a tonic signal. Ligandindependent signaling by the precursors of mature antigen receptors regulates development of B- and T-lymphocytes. Here we describe a basal signal controlling gene expression profiles in the Jurkat T cell line and mouse thymocytes. Using DNA microarrays and Northern blots to analyze unstimulated cells, we demonstrate that expression of a cluster of genes, including RAG-1 and RAG2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76. This TCR-like pathway results from constitutive low-level activity of Erk and Abl kinases. Inhibition of Abl by the drug STI-571 or events upstream of Erk increases RAG-1 expression. Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation.
2005-10-14 | E-SMDB-2194 | biostudies-arrayexpress
Project description:The goals of this study were to identify gene transcription changes in cells expressing activated H-RasV12 or activated versions of the ras effector domain mutants RasV12G37, RasV12S35, and RasV12C40 for the purpose of identifying common or unique transcription alterations in cells transformed by different ras signal transduction pathways. Keywords: genetic modification design
2008-08-01 | GSE8916 | GEO
Project description:Palmitoylation is the reversible addition of palmitate to cysteine via a thioester linkage. The reversible nature of this modification makes it a prime candidate as a mechanism for regulating signal transduction in T-cell receptor signaling. Following stimulation of the T-cell receptor we find a number of proteins are newly palmitoylated, including those involved in vesicle-mediated transport and Ras signal transduction. Among these stimulation-dependent palmitoylation targets are the v-SNARE VAMP7, important for docking of vesicular LAT during TCR signaling, and the largely undescribed palmitoyl acyltransferase DHHC18 that is expressed in two isoforms in T cells. Using our newly developed On-Plate Palmitoylation Assay (OPPA), we show DHHC18 is capable of palmitoylating VAMP7 at Cys183. Cellular imaging shows that the palmitoylation-deficient protein fails to be retained at the Golgi.
2021-09-09 | PXD018703 | Pride
Project description:Extracellular superoxide dismutase (SOD3), which dismutases hydrogen peroxide to superoxide anion at cell membranes, mimics RAS oncogene action inducing primary cell immortalization at sustained low-level expression while high expression activates cancer barrier signaling through p53-p21 growth arrest pathway. We have previously demonstrated that the growth regulation of SOD3 occurs at the level of RAS and is mediated through non-transcriptional and transcriptional routes. Therefore, in the current work we assayed the growth suppressive mechanisms of SOD3 by characterizing the main signal transduction routes from the cell membrane into the nucleus. Based on our data robust over-expression of SOD3 in anaplastic thyroid cancer 8505c cells increased EGFR, RYK, ALK, FLT3, and EPHA10 tyrosine kinase receptor phosphorylation with consequent downstream SRC, FYN, YES, HCK, and LYN kinase activation. However, RAS pull-down experiment suggested lack of mitogen pathway stimulation that was confirmed by MEK1/2 and ERK1/2 Western blot. Interestingly, mRNA expression analysis indicated that SOD3 regulated in a dose dependent manner the expression of selected guanine nucleotide exchange factors (Rho GEF16, Ral GEF RGL1), GTPase activating proteins (ArfGAP ADAP2, Ras GAP RASAL1, RGS4), and Rho guanine nucleotide disassociation inhibitors (Rho GDI 2) therefore controlling the signal transduction through RAS GTPases to downstream signal transduction pathways. Our current data suggests a SOD3-induced activation of growth signal transduction is controlled in a dose dependent manner through GEF, GAP, and GDI.
2014-12-31 | GSE56546 | GEO