Expression data from MOLM-14 human acute myeloid leukemia cell line after AMPK activation by GSK621 according to mTORC1 activation level
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE68209 | GEO | 2016/04/22
SECONDARY ACCESSION(S): PRJNA282029
REPOSITORIES: GEO
Similar Datasets
Project description:The objective of the sudy is to evalute the role of mTORC1 signalling in the regulation of the metabolism of MOLM-14 cells. We used microarrays to investigate gene expression in MOLM-14 cells after down-regulation of mTORC1 signalling by rapamycin.
2017-08-14 | GSE95172 | GEO
Project description:Pancreatic beta cells (β-cells) differentiate during fetal life, but only postnatally acquire the capacity for glucose-stimulated insulin secretion (GSIS). The molecular mechanisms driving this maturation of β-cell function remain incompletely understood. Here, we show that the control of cellular signaling in β-cells fundamentally switches from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK), and that this is critical for functional maturation. Moreover, AMPK is activated by the dietary transition taking place during weaning, and this in turn inhibits mTORC1 activity to drive the adult β-cell phenotype. While forcing constitutive mTORC1 signaling in adult β-cells relegates them to a functionally immature phenotype with characteristic transcriptional and metabolic profiles, engineering the switch from mTORC1 to AMPK signaling is sufficient to promote β-cell mitochondrial biogenesis, a shift to oxidative metabolism, and functional maturation. We also show that type 2 diabetes, a condition marked by both mitochondrial degeneration and dysregulated GSIS, is associated with a remarkable reversion of the normal AMPK-dependent adult β-cell signature to a more neonatal one characterized by mTORC1 activation. Manipulating the way in which cellular nutrient signaling pathways regulate β-cell metabolism may thus offer new targets to improve β-cell function in diabetes.
2019-06-06 | GSE132261 | GEO
Project description:Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational–experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes.
2016-12-12 | PXD003073 | Pride
Project description:DallePezze2016 - Activation of AMPK and mTOR
by amino acids (Model 3)
This model is as described in
the Supplementary Software 3 of the reference publication: SBML
model similar to Model S2, but including a more complex p70-S6K
module.
This model is described in the article:
A systems study reveals
concurrent activation of AMPK and mTOR by amino acids.
Dalle Pezze P, Ruf S, Sonntag AG,
Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van
Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B,
Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn
U, Horvatovich P, Shanley DP, Thedieck K.
Nat Commun 2016 Nov; 7: 13254
Abstract:
Amino acids (aa) are not only building blocks for proteins,
but also signalling molecules, with the mammalian target of
rapamycin complex 1 (mTORC1) acting as a key mediator. However,
little is known about whether aa, independently of mTORC1,
activate other kinases of the mTOR signalling network. To
delineate aa-stimulated mTOR network dynamics, we here combine
a computational-experimental approach with text mining-enhanced
quantitative proteomics. We report that AMP-activated protein
kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR
complex 2 (mTORC2) are acutely activated by aa-readdition in an
mTORC1-independent manner. AMPK activation by aa is mediated by
Ca2+/calmodulin-dependent protein kinase kinase ? (CaMKK?). In
response, AMPK impinges on the autophagy regulators Unc-51-like
kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an
mTORC1 antagonist that is activated by starvation. We find that
aa acutely activate AMPK concurrently with mTOR. We show that
AMPK under aa sufficiency acts to sustain autophagy. This may
be required to maintain protein homoeostasis and deliver
metabolite intermediates for biosynthetic processes.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000640.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-05-07 | BIOMD0000000640 | BioModels
Project description:DallePezze2016 - Activation of AMPK and mTOR
by amino acids (Model 1)
This model is as described in
Supplementary Software 2 of the reference publication:
SBML
model including only the canonical amino acid input on
mTORC1.
This model is described in the article:
A systems study reveals
concurrent activation of AMPK and mTOR by amino acids.
Dalle Pezze P, Ruf S, Sonntag AG,
Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van
Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B,
Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn
U, Horvatovich P, Shanley DP, Thedieck K.
Nat Commun 2016 Nov; 7: 13254
Abstract:
Amino acids (aa) are not only building blocks for proteins,
but also signalling molecules, with the mammalian target of
rapamycin complex 1 (mTORC1) acting as a key mediator. However,
little is known about whether aa, independently of mTORC1,
activate other kinases of the mTOR signalling network. To
delineate aa-stimulated mTOR network dynamics, we here combine
a computational-experimental approach with text mining-enhanced
quantitative proteomics. We report that AMP-activated protein
kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR
complex 2 (mTORC2) are acutely activated by aa-readdition in an
mTORC1-independent manner. AMPK activation by aa is mediated by
Ca2+/calmodulin-dependent protein kinase kinase ? (CaMKK?). In
response, AMPK impinges on the autophagy regulators Unc-51-like
kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an
mTORC1 antagonist that is activated by starvation. We find that
aa acutely activate AMPK concurrently with mTOR. We show that
AMPK under aa sufficiency acts to sustain autophagy. This may
be required to maintain protein homoeostasis and deliver
metabolite intermediates for biosynthetic processes.
This model is hosted on
BioModels Database
and identified by:
MODEL1705030000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-05-18 | MODEL1705030000 | BioModels
Project description:Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a M-bM-^@M-^\low/low/high/lowM-bM-^@M-^] or M-bM-^@M-^\LLHLM-bM-^@M-^]. We found that mTORC1 regulated the expression of, among other lysosomal genes, V-ATPases through the transcription factor EB (TFEB, Tcfeb in the mouse). The knockdown of Tfeb resulted in the 'flattening' of the LLHL pattern and allowed the identification of genes regulated by mTORC1 through Tfeb Mouse embryo fibroblasts (MEFs) wild type or deficient in Tsc2 expressing a Tfeb shRNA or scrambled shRNA vector were treated with 25 nM rapamycin or vehicle (methanol) for 24 h under low serum conditions (0.1% FBS)
2011-08-02 | E-GEOD-28021 | biostudies-arrayexpress
Project description:DallePezze2016 - Activation of AMPK and mTOR
by amino acids (Model 2)
This
model is as described in the Supplementary Software 2 of the
reference publication:
SBML
model including four amino acids input in the network (simple
p70-S6K module).
This model is described in the article:
A systems study reveals
concurrent activation of AMPK and mTOR by amino acids.
Dalle Pezze P, Ruf S, Sonntag AG,
Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van
Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B,
Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn
U, Horvatovich P, Shanley DP, Thedieck K.
Nat Commun 2016 Nov; 7: 13254
Abstract:
Amino acids (aa) are not only building blocks for proteins,
but also signalling molecules, with the mammalian target of
rapamycin complex 1 (mTORC1) acting as a key mediator. However,
little is known about whether aa, independently of mTORC1,
activate other kinases of the mTOR signalling network. To
delineate aa-stimulated mTOR network dynamics, we here combine
a computational-experimental approach with text mining-enhanced
quantitative proteomics. We report that AMP-activated protein
kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR
complex 2 (mTORC2) are acutely activated by aa-readdition in an
mTORC1-independent manner. AMPK activation by aa is mediated by
Ca2+/calmodulin-dependent protein kinase kinase ? (CaMKK?). In
response, AMPK impinges on the autophagy regulators Unc-51-like
kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an
mTORC1 antagonist that is activated by starvation. We find that
aa acutely activate AMPK concurrently with mTOR. We show that
AMPK under aa sufficiency acts to sustain autophagy. This may
be required to maintain protein homoeostasis and deliver
metabolite intermediates for biosynthetic processes.
This model is hosted on
BioModels Database
and identified by:
MODEL1705030001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-05-18 | MODEL1705030001 | BioModels
Project description:Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a M-^Slow/low/high/lowM-^T or M-^SLLHLM-^T, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons
2011-08-02 | E-GEOD-27982 | biostudies-arrayexpress
Project description:To screen miRNAs specifically regulated by mTORC1 or mTORC2, a global miRNA expression profile in MCF-7 cells treated with rapamycin or PP242 (mTORC1/2 kinase inhibitor) was developed using microarray. control, rapamycin or PP242 treated human MCF-7 cells were harvested 48h post-treatment and subjected to total RNA extraction.
2014-09-11 | E-GEOD-61289 | biostudies-arrayexpress
Project description:The kinases mTORC1 and AMPK are at the nexus of nutrient responses and control of cellular growth. However, responses to nutrient loss are complex and affect multiple transcriptional pathways. We are interested in the mTORC1-directed regulation of transcription networks that specifically regulate developmental decisions. Dictyostelium grow logarithmically as single cells in nutrient-rich media, but, upon nutrient withdrawal, growth ceases and cells enter a program for multi-cellular development. Within 30 minutes of starvation, >4,000 genes show significant (p<0.05) changes in gene expression patterns. However, we hypothesize that not all these gene changes are required for development and that many expression changes reflect stress response to a media shift supplementary to nutrient loss, apart from developmental effects. We, thus, sought ways to promote development in the absence of nutrient loss, to better focus on developmentally essential gene sets. Since kinases mTORC1 and AMPK function as nutrient and energy sensors, we first examined their relative activities in Dictyostelium during phases of rapid growth and starvation-induced development. We found that these kinases exhibited reciprocal patterns of activation under various conditions. With this knowledge, we identified rich media conditions that permitted rapid cell growth, but a growth/development switch upon the directed and reciprocal inactivation/activation of mTORC1/AMPK. Examination of gene expression under conditions of development in nutrient-rich media indicated that changes in expression of most starvation-regulated genes were not required for development. Our data suggest that the up-regulation of ~300 genes defines essential early signaling pathways for developmental induction, integrating cAMP/PKA circuitries and including many unclassified genes.
2019-05-22 | GSE123599 | GEO