Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AMPKβ1/β2 isoform-specific gene expression profile in human induced pluripotent stem cells

ABSTRACT: AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that, upon activation, phosphorylates a wide range of substrate proteins in order to restore cellular energy balance. AMPK is a heterotrimeric protein that is composed of three subunits: α, β and γ. The α and β subunits are encoded by two, the γ subunit by three genes that are expressed in a tissue- and species-specific manner. However, neither the mechanisms of how different trimer combinations affect AMPK downstream effects nor the functional properties of single isoforms are completely understood so far. We provide evidence that AMPKβ1- and β2-containing AMPK trimers lead to different gene expression profiles in a model of human induced pluripotent stem cells and thereby differentially affect lineage decision. The analysis of hiPSCs harboring a gene knockout for AMPK β1 (PRKAB1-/-) and for AMPK β2 (PRKAB2-/-) compared to WT hiPSCs revealed major differences in the gene expression profile in all the cell lines. This suggests an isoform-specific regulation of gene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144043 | GEO | 2020/04/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data of beta-subunit of Snf1 kinase in yeast Saccharomyces cerevisiae

Project description:The conserved Snf1/AMPK (AMP-activated protein Kinase) family is one of the central components in nutrient sensing and regulation of carbon metabolism in eukaryotes. It is also involved in several other processes such as stress resistance, invasive growth and ageing. Snf1 kinase is composed of a catalytic alpha-subunit Snf1, a regulatory gamma-subunit Snf4 and one of three possible beta-subunits, Sip1, Sip2 or Gal83. We used a systematic approach to study the role of the three beta-subunits by analyzing all 7 possible combinations of beta-subunit deletions together with the reference strain.

2010-05-27 | E-GEOD-20591 | biostudies-arrayexpress

The γ2 subunit of AMP-activated protein kinase regulates mammalian heart rate

Project description:AMP-activated protein 1 kinase (AMPK), a phylogenetically conserved serine/threonine kinase regarded as a key cellular energy sensor, exists in eukaryotes as a heterotrimer comprising a catalytic α and regulatory β and γ subunits. In humans, activating mutations in the gene encoding the γ2 subunit of AMPK (PRKAG2) display a cardiac phenotype of left ventricular hypertrophy (LVH), conduction system disease, ventricular pre-excitation and increased cardiomyocyte glycogen accumulation. While existing transgenic models have elucidated the pathogenesis of several aspects of the disease5-7, the slow heart rate (sinus bradycardia) – a prominent feature of the disease – remains poorly understood. Here, using gene-targeting to generate mice which recapitulate this bradycardia, we demonstrate that γ2 AMPK activation perturbs fundamental mechanisms that determine sinoatrial pacemaker cell function. Reduction in the sarcolemmal hyperpolarization activated (“funny”) current (If) and damping of ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ releases (LCRs)12,13 contribute to reduced sinoatrial cell spontaneous activity and, ultimately, to a lower heart rate. Pharmacological activation of AMPK reversibly reduces the beating rate of murine pluripotent stem cell-derived induced sinoatrial bodies. In contrast, using a mouse knock-out of γ2 AMPK, which exhibits an increased heart rate, we demonstrate a role for γ2 AMPK in physiological heart rate regulation, including an indispensable role in the bradycardic adaptation to endurance exercise. Through regulating the cardiac pacemaker and thereby heart rate, γ2 AMPK by virtue of its energy-sensing role, is a key physiological determinant of overall cardiac energy homeostasis.

2017-09-30 | GSE73047 | GEO

RNA-seq of NSC-34 cells expressing SOD1

Project description:Misfolded soluble trimeric species of superoxide dismutase 1 (SOD1) are associated with increased death in neuron-like cell models and greater disease severity in amyotrophic lateral sclerosis (ALS) patients compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may be a driver of disease pathology. Here, we uncovered the SOD1 trimer transcriptome. We identified key pathways using transcriptomic data from motor neuron-like cells (NSC-34s) expressing SOD1 trimers. We discovered differential gene expression in cells that express SOD1 trimers with selective enrichment of genes responsible for protein localization to membranes and a global upregulation of cellular senescence pathways. Our investigation highlights key protein factors and pathways within each system, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.

2024-10-09 | GSE263048 | GEO

Expression data of β-subunit of Snf1 kinase in yeast Saccharomyces cerevisiae

Project description:The conserved Snf1/AMPK (AMP-activated protein Kinase) family is one of the central components in nutrient sensing and regulation of carbon metabolism in eukaryotes. It is also involved in several other processes such as stress resistance, invasive growth and ageing. Snf1 kinase is composed of a catalytic α-subunit Snf1, a regulatory γ-subunit Snf4 and one of three possible β-subunits, Sip1, Sip2 or Gal83. We used a systematic approach to study the role of the three β-subunits by analyzing all 7 possible combinations of β-subunit deletions together with the reference strain.

2010-05-10 | GSE20591 | GEO

Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry

Project description:CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase (CS), with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange mass spectrometry to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intra-trimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a longer-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a non-random orientation. These results provide new molecular insights into the allosteric formation of the CS complex and could help guide antibacterial drug design.

2021-06-07 | PXD025300 | Pride

Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes

Project description:Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes. Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride levels in adipocytes. AMP-activated protein kinase (AMPK) was recently demonstrated to be involved in the emerging pathways regulating this response. This study investigated the role of AMPK and inflammation in lowering triglyceride levels by testing the following hypotheses: 1) A moderate activator of AMPK, such as metformin, and an inflammatory response are sufficient to reduce triglycerides, and 2) Strong activation of AMPK is also sufficient. These experiments were performed by adding compounds that affect these pathways and measuring their effects in 3T3-L1 adipocytes. Tumor necrosis factor α (TNF-α), an inflammatory cytokine, increased the ability of metformin to reduce triglycerides, but TNF-α was observed to activate AMPK. A comparison of metformin, phenformin, TNF-α, and t10c12 CLA found a correlation between AMPK activity level and triglyceride reduction. Inhibitors of the prostaglandin (PG) biosynthetic pathway interfered with t10c12 CLA's ability to reduce triglycerides. Inhibitors of MAPK/ERK kinase or Jun N-terminal kinase interfered with the phosphorylation of phospholipase A2 and triglyceride reductions. Keywords: control/treatment Mouse 3T3-L1 RNA was isolated from control (LA) and treatment (CLA, phenformin) samples for analysis on microarrays with three biological replicates per sample. Limma data are available in the Supplementary files 'GSE17404_limma_CLAvsLA.txt', 'GSE17404_limma_PFMvsLA.txt', and 'GSE17404_limma_PFMvsCLA.txt'.

2010-08-10 | E-GEOD-17404 | biostudies-arrayexpress

Intact Transition Epitope Mapping - Forces of Interactions between Variants of Equivalent macromolecules (ITEM-FIVE)

Project description:Foldon (F) is a specific partial sequence from the C-terminal domain of T4 fibritin, which is found at the neck of the T4 bacteriophage. The amino acid sequence (27 residues) in single letter code is GYIPEAPRDGQAYVRKDGEWVLLSTFL. In neutral solution (pH 6.9) it forms a homo-trimer (F-F-F). Biotinylated foldon (bF) is composed of the exact same amino acid sequence but contains a biotin residue attached to the N-terminal amino acid residue via two PEG linker molecules. In solution with neutral pH it forms a homo-trimer (bF-bF-bF). Mixing of both homo-trimers in solution with neutral pH spontaneously produces hetero-trimers (F-F-bF and F-bF-bF).

2024-04-29 | PXD044721 | Pride

Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes

2010-08-10 | GSE17404 | GEO

Adenosine 5â monophosphate-activated protein kinase regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 mitogen-activated protein kinase.

Project description:Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, while AMPK is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive GILZ, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Since increased action of glucocorticoids is associated with development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacologic interventions to these pathologies. We tested the hypothesis by treateing rats with the synthetic glucocorticoid dexamethasone and the AMPK activator 5-aminoimidazole-4-carboxamide-1-Î²-d-ribonucleoside (AICAR).

2010-07-30 | E-GEOD-22647 | biostudies-arrayexpress

Transcriptional profiling of Ampk-deficient B cells during terminal differentiation

Project description:5’-AMP-Activated Protein Kinase (Ampk) is an energy gatekeeper that responds to decreases in available ATP by inhibiting energy-consuming processes like protein synthesis and promoting energy-generating processes like glucose uptake. Recently, our lab showed that Lkb1, a previously unstudied kinase in B cell immunology and the main upstream kinase of Ampk, had a critical and unexpected role in B cell activation and germinal center formation. In T cells knockout of the downstream target Ampk, only partially phenocopies Lkb1 deletion, so we sought to determine whether the role of Lkb1 in B cells depends on Ampk. We find Ampk is activated upon B cell stimulation in vitro. Surprisingly, however, Ampk activation occurs in the absence of energetic stress, and B cells continue to grow and divide despite Ampk activity. We performed an IP-MS substrate screen to identify Ampk targets and only identified a limited repertoire of canonical targets, and many non-canonical targets. Despite activation of Ampk and the major role of Lkb1 in B cell activation, B cell specific deletion of Ampk does not significantly affect B cell activation, differentiation, carbon handling, gene expression, or humoral immune responses. The only major effect of Ampk loss was accelerated downregulation of IgD during stimulation, which was preceded by downregulation of the IgD regulator Zfp318. Early activation of Ampk by pharmacological means also has little impact on B cell function, although treatment with the biguanide Phenformin critically impairs germinal center formation and class switch recombination in vivo, but does not significantly impair antigen-specific antibody responses. Combined, our results suggest an unexpected and unexplained activation of Ampk in B cells.

2019-06-16 | GSE121025 | GEO

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