Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from control and Phospholipid dependent kinase 1 (PDK1) null cytotoxic T-lymphocytes (CTL) and from control and Akt inhibitor treated CTL

ABSTRACT: In cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1). The role of PDK1 and Akt in CTL has however not been fully defined. In order to explore the relative roles of these kinases in CTL we used microarrays to profile the gene expression of control and PDK1 null CTL. In separate experiments we compared the gene expression profiles of control and Akt inhibitor treated CTL. CTL were generated from 3 mice each carrying two loxP flanked PDK1 alleles plus a tamoxifen inducible Cre transgene. PDK1 was then deleted from these CTL by tamoxifen treatment and the gene expression pattern determined by microarray. Tamoxifen treated PDK1wt/wt TamoxCre+ CTL generated from 3 PDK1wt/wt TamocCre+ mice were used as a control. In separate experiments CTL were were generated from 3 wild-type mice and then half the CTL generated from each mouse were treated with the Akt inhibitor AktI-1/2. The gene expression patterns of the AktI treated and the untreated CTL were then compared by microarray.

ORGANISM(S): Mus musculus

SUBMITTER: maria feijoo

PROVIDER: E-GEOD-26290 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression data from control and Phospholipid dependent kinase 1 (PDK1) null cytotoxic T-lymphocytes (CTL) and from control and Akt inhibitor treated CTL

Project description:In cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1). The role of PDK1 and Akt in CTL has however not been fully defined. In order to explore the relative roles of these kinases in CTL we used microarrays to profile the gene expression of control and PDK1 null CTL. In separate experiments we compared the gene expression profiles of control and Akt inhibitor treated CTL.

2011-02-01 | GSE26290 | GEO

Effect of rapamycin and KU-0063794 on CTL gene expression

Project description:Comparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis. Abstract: High resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTL. We show that the CTL proteome is dominated by metabolic regulators and granzymes and that mTORC1 selectively represses and promotes expression of a protein subset (~10%) including key CTL effector molecules and signaling proteins. mTORC1 also controlled flux through a subset of metabolic pathways rather than acting as an on/off switch for global CTL metabolism. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production in CTL. Further work revealed that mTORC1 represses PIP3 production and determines the mTORC2 requirement for activation of the serine/threonine kinase AKT. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function.

2015-07-15 | GSE70925 | GEO

CTL differentiation: WT vs. IL-2Ra deficient CTL

Project description:Gene expression analysis of WT and IL-2Ra-deficient CTL (P14) isolated 8 days after inffection with LCMV. The goals of the study are to assess the impact of IL-2 signals on effector and memory CTL differentiation.

2009-12-23 | GSE19598 | GEO

MITOCHONDRIAL Akt REGULATION OF HYPOXIC METABOLIC REPROGRAMMING

Project description:Hypoxia is a driver of aggressive tumor behavior, but the mechanisms are not completely understood. In a global phosphoproteomics screen, we now demonstrate that hypoxia induces the recruitment of Akt2 to tumor mitochondria, and Akt phosphorylation of pyruvate dehydrogenase kinase (PDK1) on Thr346. In turn, Akt-phosphorylated PDK1 shuts off oxidative phosphorylation via phosphorylation of the pyruvate dehydrogenase complex, and reprograms tumor metabolism towards glycolysis. Akt-phosphorylation of PDK1 is required to prevent autophagy, maintain cell viability and support tumor cell proliferation in hypoxia, in vivo. Therefore, mitochondrial Akt is a pathophysiologic switch for tumor adaptation in hypoxia.

2016-04-20 | MSV000079671 | MassIVE

Inhibition of AKT-signaling uncouples cellular differentiation from expansion for receptor-engineered T cells

Project description:Adoptive immunotherapies using genetically-redirected T cells expressing a chimeric antigen receptor (CAR) or T cell receptor (TCR) are poised to enter mainstream clinical practice. Despite encouraging results, some patients fail to respond to current therapies. In part, this phenomenon has been associated with infusion of a reduced number of early memory T cells. Herein, we report that pharmacologic disruption of AKT-signaling (AKTi) is compatible with the transduction of both CARs and TCRs into human T cells and promotes a minimally differentiated CD62L-expressing phenotype. Critically, this intervention did not compromise cell yield. Mechanistically, disruption of AKT-signaling preserved MAPK activation and promoted the intra-nuclear accumulation of FOXO1, a key transcriptional regulator of T-cell memory. Consequently, AKTi synchronized the T-cell transcriptional profile for FOXO1-dependent target genes across multiple donors. Expression of an AKT-resistant FOXO1 mutant phenocopied the influence of AKTi while addition of AKTi to T cells expressing mutant FOXO1 failed to further augment the frequency of CD62L-expressing cells. Finally, CD19 CAR-modified T cells transduced and expanded in AKTi treated established B-cell acute lymphoblastic leukemia superiorly to conventionally grown T cells in a murine xenograft model. Thus, inhibition of AKT-signaling represents a generalizable strategy to generate large numbers of receptor-modified T cells with an early memory phenotype.

2018-02-16 | GSE98078 | GEO

Expression data from CTL and Tc17 cell

Project description:Goal of this study was to compare transcriptional changes in CTL cells compared to Tc17 cells We used microarray to detail the global programme of gene expression underlying CTL and Tc17 cell differentiation and identified distinct classes of upregulated genes thereby

2018-02-09 | GSE110346 | GEO

S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions

Project description:Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Mechanistically, S6K1-mediated phosphorylation of PDK1 augments its interaction with 14-3-3 adaptor protein and homo-dimerization, subsequently dissociating PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP3) and retarding its interaction with AKT. Pathologically, tumor patient-associated PDK1 mutations, either attenuating S6K1-mediated PDK1 phosphorylation or impairing PDK1 interaction with 14-3-3, result in elevated AKT kinase activity and oncogenic functions. Taken together, our findings not only unravel a delicate feedback regulation of AKT signaling via S6K1-mediated PDK1 phosphorylation, but also highlight the potential strategy to combat mutant PDK1-driven cancers.

2021-08-27 | PXD028167 | iProX

High Glucose (HG) treated morula vs control glucose (CTL) treated morula

Project description:Early bovine cleavage (day 0 to 3) was treated with high glucose (5mM) or control glucose (0.2mM) then total day 3 embryos were cultured in control condition until day 5 when gene expression was assessed in developping morula by microarray 4 replicates of 10 morulae/rep was produced for high glucose and control treatment. According to a dye swap design, 4 arrays were used, one array for each comparison between HG and control, i.e replicate 1 from HG were compared to replicate 1 from CTL, rep 2 from HG were compared to rep 2 from CTL, rep 3 HG vs rep 3 CTL, rep 4 HG vs rep 4 CTL.

2012-09-01 | E-GEOD-40521 | biostudies-arrayexpress

Mus musculus

Project description:Expression data from control and Phospholipid dependent kinase 1 (PDK1) null cytotoxic T-lymphocytes (CTL) and from control and Akt inhibitor treated CTL

| PRJNA135051 | ENA

Effect of IL-12 on CTL gene expression

Project description:The goal was to determine how IL-12 affects gene expression by murine CTL.

2009-02-01 | GSE13173 | GEO