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AKT1S1 — MTOR
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
mTORC1 complex (MTOR-MLST8-RPTOR)
→
PRAS40 (AKT1S1)
(modification, collaborate)
Takeuchi et al., J Biol Chem 2001, Moumen et al., Development 2007
Evidence: mutant phenotype
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
mTORC1 complex (MTOR-MLST8-RPTOR)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Takeuchi et al., J Biol Chem 2001, Moumen et al., Development 2007
Evidence: mutant phenotype
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
DEPTOR (DEPTOR)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Takeuchi et al., J Biol Chem 2001, Moumen et al., Development 2007
Evidence: mutant phenotype
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
PRAS40 (AKT1S1)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Takeuchi et al., J Biol Chem 2001, Moumen et al., Development 2007
Evidence: mutant phenotype
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
→
AKT1-2-active (AKT1/AKT2)
(modification, collaborate)
Takeuchi et al., J Biol Chem 2001, Moumen et al., Development 2007
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
mTOR/GBL/PRAS40/DEPTOR complex (MTOR-MLST8-DEPTOR-AKT1S1)
→
RAPTOR (RPTOR)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTOR/GBL/PRAS40/DEPTOR complex (MTOR-MLST8-DEPTOR-AKT1S1)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTOR/GBL/PRAS40/DEPTOR complex (MTOR-MLST8-DEPTOR-AKT1S1)
→
None
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
RAPTOR (RPTOR)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database LKB1 signaling events:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
mTORC1 complex complex (MTOR-MLST8-RPTOR-AKT1S1)
(modification, collaborate)
Shaw et al., Cancer Cell 2004, Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database LKB1 signaling events:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
mTORC1 complex/14-3-3 family complex (MTOR-MLST8-RPTOR-AKT1S1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, collaborate)
Shaw et al., Cancer Cell 2004, Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database LKB1 signaling events:
mTORC1 complex complex (MTOR-MLST8-RPTOR-AKT1S1)
→
mTORC1 complex/14-3-3 family complex (MTOR-MLST8-RPTOR-AKT1S1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, collaborate)
Shaw et al., Cancer Cell 2004, Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
RagA-B/GTP/RagC-D/GDP complex (RRAGA_RRAGB-RRAGC_RRAGD)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, activates)
Sancak et al., Science 2008, Kim et al., Nat Cell Biol 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
PML (PML)
→
mTORC1/PRAS40/DEPTOR/PML complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR-PML)
(modification, collaborate)
Bernardi et al., Nature 2006
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
PML (PML)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Bernardi et al., Nature 2006
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1/PRAS40/DEPTOR/PML complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR-PML)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Bernardi et al., Nature 2006
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database LKB1 signaling events:
AMPKK1-AMPKK2-active ()
→
mTORC1 complex complex (MTOR-MLST8-RPTOR-AKT1S1)
(modification, activates)
Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay
-
NCI Pathway Database mTOR signaling pathway:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
mTORC1/PRAS40/DEPTOR/14-3-3 family complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, collaborate)
Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
→
mTORC1/PRAS40/DEPTOR/14-3-3 family complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, collaborate)
Gwinn et al., Mol Cell 2008
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, collaborate)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
PRAS40 (AKT1S1)
(modification, collaborate)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
AKT1 (AKT1)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, activates)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
RHEB/GTP complex (RHEB)
→
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
(modification, activates)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
→
DEPTOR (DEPTOR)
(modification, collaborate)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR)
→
PRAS40 (AKT1S1)
(modification, collaborate)
Garami et al., Mol Cell 2003, Inoki et al., Genes Dev 2003, Vander Haar et al., Nat Cell Biol 2007, Sancak et al., Mol Cell 2007, Wang et al., J Biol Chem 2007, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
Reactome Reaction:
MTOR
→
AKT1S1
(direct_complex)
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
AKT1S1
→
MLST8/MTOR/RPTOR
(inhibition)
-
WikiPathways Senescence and Autophagy in Cancer:
MTOR
→
AKT1S1
(unknown)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
AKT1S1
—
MTOR
(physical association, affinity chromatography technology)
Sancak et al., Mol Cell 2007
-
IRef Biogrid Interaction:
AKT1S1
—
MTOR
(physical association, affinity chromatography technology)
Peterson et al., Cell 2009
-
IRef Hprd Interaction:
AKT1S1
—
MTOR
(in vivo)
Vander Haar et al., Nat Cell Biol 2007
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Vander Haar et al., Nat Cell Biol 2007
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Thedieck et al., PloS one 2007*
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Oshiro et al., J Biol Chem 2007*
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Fonseca et al., J Biol Chem 2007*
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Hong et al., Mol Cell 2008*
-
IRef Innatedb Interaction:
AKT1S1
—
MTOR
(unknown, -)
Toschi et al., Mol Cell Biol 2009
-
IRef Intact Interaction:
Complex of RPTOR-AKT1S1-MTOR
(physical association, anti tag coimmunoprecipitation)
Peterson et al., Cell 2009
Text-mined interactions from Literome
Hayashi et al., Am J Physiol Endocrinol Metab 2007
:
Consistent with this, GH increased the phosphorylation of
TSC2 , an upstream
regulator of
mTORC1 , at sites that are targets for Akt/PKB
Sancak et al., Mol Cell 2007
:
Insulin stimulates Akt/PKB mediated phosphorylation of PRAS40, which prevents its inhibition of
mTORC1 in cells and in vitro
Wang et al., J Biol Chem 2007
:
In
response to
insulin and nutrients,
mTORC1 , consisting of mTOR, raptor ( regulatory associated protein of mTOR ), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein ( 4EBP ) and p70 S6 kinase to promote protein synthesis and cell size
Akcakanat et al., Biochem Biophys Res Commun 2007
:
mTORC1 is rapamycin-sensitive, and
results in phosphorylation of 4E-BP1 and
S6K1 ...
mTORC1 is rapamycin-sensitive, and
results in phosphorylation of
4E-BP1 and S6K1
Averous et al., Oncogene 2008
(Breast Neoplasms) :
Regulation of
cyclin D1 expression by
mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1
Harwood et al., J Biol Chem 2008
(MAP Kinase Signaling System) :
mTORC1 signaling can
regulate growth factor activation of
p44/42 mitogen activated protein kinases through protein phosphatase 2A ...
mTORC1 signaling can
regulate growth factor activation of
p44/42 mitogen activated protein kinases through protein phosphatase 2A ... However, a
role for
mTORC1 signaling in modulating activation of
p44/42 has not been reported ... However, a
role for
mTORC1 signaling in modulating activation of
p44/42 has not been reported
Vojtechová et al., Neoplasia (New York, N.Y.) 2008
:
Regulation of
mTORC1 signaling by
Src kinase activity is Akt1 independent in RSV transformed cells
Mills et al., Proc Natl Acad Sci U S A 2008
(Lymphoma) :
Here, we demonstrate that loss of
TSC2 in the E mu-myc murine lymphoma model
leads to
mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation
Wang et al., J Biol Chem 2008
:
Reducing
TCTP levels did not reproducibly
affect mTORC1 signaling in amino acid-replete/insulin stimulated cells ... Our data also indicate that, in the mammalian cell lines tested here, neither
TCTP nor FKBP38
regulates mTORC1 signaling ... Our data also indicate that, in the mammalian cell lines tested here, neither TCTP nor
FKBP38 regulates
mTORC1 signaling
Carracedo et al., J Clin Invest 2008
(MAP Kinase Signaling System...) :
Taken together, our findings identify
MAPK activation as a
consequence of
mTORC1 inhibition and underscore the potential of a combined therapeutic approach with mTORC1 and MAPK inhibitors, currently employed as single agents in the clinic, for the treatment of human cancers
Avruch et al., Am J Physiol Endocrinol Metab 2009
:
Insulin , growth factors, and a variety of cellular stressors
regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein ... In contrast, amino acids, especially leucine,
regulate mTORC1 by controlling the ability of Rheb-GTP to activate
mTORC1
Wang et al., Oncogene 2008
(Prostatic Neoplasms) :
Inhibition of both
mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity
resulted from the inhibition of mTORC1, but not
mTORC2 ... Inhibition of both
mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity
resulted from the inhibition of
mTORC1 , but not mTORC2
Karni et al., Proc Natl Acad Sci U S A 2008
:
mTORC1 activation by
SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF in vitro and in vivo
Stevens et al., J Biol Chem 2009
:
DAPK ( +/- ) mouse embryo fibroblasts have attenuated mTORC1 signaling compared with DAPK+/+ counterparts, and overexpression of
DAPK in DAPK ( +/- ) MEFs
stimulates mTORC1 activity
Rahimi et al., Cancer Res 2009
:
mTORC2 promotes TGF-beta induced morphologic transformation and is
required for TGF-beta induced Akt S473 phosphorylation but not
mTORC1 activation
Lorne et al., Am J Respir Cell Mol Biol 2009
(Acute Lung Injury) :
Rapamycin pretreatment inhibited PAM- or
LPS induced
mTORC1 activation in the lungs
Ikenoue et al., Methods Enzymol 2009
:
In turn,
mTORC1 regulates the activity of the translational machinery by modulating S6 kinase ( S6K ) activity and
eIF4E binding protein 1 ( 4E-BP1 ) through direct phosphorylation
Uhlenbrock et al., FEBS Lett 2009
:
Recent studies document that
Rheb activates
mTORC1 via direct, GTP dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1
Dunlop et al., Cell Signal 2009
:
Finally, we show that activation of
mTORC1 by both Rheb and RhebL1 is
impaired by
FKBP38 ... Finally, we show that
activation of
mTORC1 by both
Rheb and RhebL1 is impaired by FKBP38 ... Finally, we show that
activation of
mTORC1 by both Rheb and
RhebL1 is impaired by FKBP38
Sato et al., J Biol Chem 2009
:
The
activation of
mTORC1 by
Rheb can be faithfully reproduced in vitro by using mTORC1 immunoprecipitated by the use of anti-raptor antibody from mammalian cells starved for nutrients
Breuleux et al., Mol Cancer Ther 2009
(Neoplasms) :
RAD001 ( everolimus ), an
mTORC1 ( mTOR/raptor )
inhibitor , has broad antitumor activity in preclinical models and cancer patients
Peterson et al., Cell 2009
(Multiple Myeloma) :
Loss of
DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and
activates mTORC1 and mTORC2 kinase activities
James et al., Mol Cell Biol 2009
(Meningioma...) :
Merlin does not
regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen activated protein kinase/extracellular signal regulated kinase mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion ... Merlin does not regulate
mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or
mitogen activated protein kinase/extracellular signal
regulated kinase mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion
Baum et al., Am J Physiol Endocrinol Metab 2009
:
Compared with control livers,
insulin stimulated Akt phosphorylation and
mTORC1 signaling, as assessed by increased phosphorylation of the mTORC1 targets eIF4E binding protein ( 4E-BP ) 1 and ribosomal protein S6 kinase (S6K)1, and promoted assembly of the eIF4G x eIF4E complex
Wang et al., J Biol Chem 2009
:
Inhibition of
mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK
caused moderately enhanced
Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy
Villanueva et al., Endocrinology 2009
:
To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the
mTORC1 dependent phosphorylation of
ribosomal protein S6 (pS6)
Dibble et al., Mol Cell Biol 2009
:
We find that Rictor-T1135 is directly phosphorylated by the
mTORC1 dependent kinase
S6K1
Boletta et al., PathoGenetics 2009
:
The
mTORC1 complex regulates cell growth ( size ), proliferation, translation and autophagy, and
mTORC2 regulates the actin cytoskeleton and apoptosis
Foster et al., J Biol Chem 2010
(MAP Kinase Signaling System) :
These data suggest that
mTORC1 activation
leads to
raptor multisite phosphorylation and that raptor Ser ( 863 ) phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation ( e.g. on Ser ( 859 ) and Ser ( 855 ) )
Julien et al., Mol Cell Biol 2010
:
We found that
Rictor phosphorylation
requires mTORC1 activity and, more specifically, the p70 ribosomal S6 kinase 1 ( S6K1 )
Roca et al., Neoplasia (New York, N.Y.) 2009
(Prostatic Neoplasms) :
D942, a pharmacological activator of AMPK, stunted
CCL2 induced
mTORC1 activity, survivin expression, and cell survival without significantly affecting Akt activity
Vega-Rubin-de-Celis et al., Biochemistry 2010
:
mTORC1 is
regulated by the small GTPase
Rheb , which in turn is regulated by the GTPase activating protein complex, TSC1/TSC2
Horak et al., Proc Natl Acad Sci U S A 2010
(Cell Transformation, Viral...) :
Surprisingly, however,
HIF-1 up-regulation in REDD1 ( -/- ) cells is largely
independent of
mTORC1 activity
Wagner et al., Am J Physiol Cell Physiol 2010
:
Notably,
mTORC1 activity was elevated in VSMC isolated from an intimal hyperplastic patient lesion compared with normal media, and lovastatin treatment
inhibited mTORC1 activity in these cultures
Chen et al., Dev Cell 2010
:
Activated
FoxO1 inhibits
mTORC1 by TSC2 dependent and TSC2 independent mechanisms ...
Sesn3 , in turn,
inhibits mTORC1 activity in Tsc2-proficient cells ... Thus, under stress conditions,
FoxO inhibits the anabolic activity of
mTORC1 , a major consumer of cellular energy, while activating Akt, which increases cellular energy metabolism, thereby maintaining cellular energy homeostasis
Timmerman et al., J Clin Endocrinol Metab 2010
:
During insulin infusion, blood flow and capillary recruitment increased in the control ( P < 0.05 ) group only ;
Akt phosphorylation and glucose uptake
increased in both groups ( P < 0.05 ), with no group differences ; and
mTORC1 signaling increased more in control ( P < 0.05 ) than in L-NMMA
Michels et al., Mol Cell Biol 2010
:
Our results describe molecular mechanisms by which
mTORC1 controls human
MAF1 , a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1
Suryawan et al., J Appl Physiol 2010
:
Our results suggest that the enhanced activation of
mTORC1 in muscle of neonatal pigs is in part
due to regulation by PRAS40,
PLD1 , and the Rag GTPases ... Our results suggest that the enhanced activation of
mTORC1 in muscle of neonatal pigs is in part
due to regulation by PRAS40,
PLD1 , and the Rag GTPases
Wong et al., Curr Opin Pharmacol 2010
(Metabolic Diseases) :
SREBP-1c can be
induced by
mTORC1 , bifurcating lipogenesis from AKT activated gluconeogenesis
Liu et al., J Biol Chem 2010
:
Taken together, our studies reveal that RSV
inhibits leucine stimulated
mTORC1 activation by promoting
mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity ... Taken together, our studies reveal that RSV
inhibits leucine stimulated
mTORC1 activation by promoting
mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity
Rothbart et al., Cancer Res 2010
:
Whereas
AMPK activation
resulted in marked inhibition of
mTORC1 , other targets of AMPK were phosphorylated that were not mTORC1 dependent
Lee et al., PloS one 2010
(Endotoxemia) :
Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of
mTORC1-S6K still occurs in the
presence of
PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways ... Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of
mTORC1-S6K still occurs in the
presence of
PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways ... Furthermore, in vitro cellular studies demonstrated that
LPS ( lipopolysaccharide )
activation of
mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways
Zou et al., Dev Cell 2011
:
Our study demonstrates that
Rheb1 is
essential for
mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability
Real et al., PloS one 2011
:
The
effect of
E2F1 on the activation of
mTORC1 does not depend on Akt
Chong et al., Oxidative medicine and cellular longevity 2010
(Neurodegenerative Diseases) :
The function of
mTOR signaling is
mediated primarily through two mTOR complexes :
mTORC1 and mTORC2
Chao et al., J Agric Food Chem 2011
(Glioblastoma) :
Activation of
AMPK induces a-mangostin mediated phosphorylation of raptor, which subsequently associates with 14-3-3? and
results in the loss of
mTORC1 activity
Zheng et al., Nat Cell Biol 2011
:
Phosphorylation of
Rheb at Ser 130 by PRAK impairs the nucleotide binding ability of Rheb and
inhibits Rheb mediated
mTORC1 activation
Wolff et al., Mol Cell Biol 2011
(Anoxia) :
We previously reported that
mTORC1 regulation by hypoxia
involves Redd1 and the
Tsc1/Tsc2 complex ... We previously reported that
mTORC1 regulation by hypoxia
involves Redd1 and the Tsc1/Tsc2 complex
Dormond-Meuwly et al., Biochem Biophys Res Commun 2011
(Neoplasms...) :
Taken together these results show that blocking
mTORC1 in endothelial cells
activates MAPK and that a combined inhibition of MAPK and mTOR has additive anti-angiogenic effects
Dunlop et al., Autophagy 2011
:
ULK1 inhibits
mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding ... ULK1 inhibits
mTORC1 signaling,
promotes multisite
Raptor phosphorylation and hinders substrate binding ... We propose a new mechanism whereby
ULK1 contributes to
mTORC1 inhibition through hindrance of substrate docking to Raptor
Saci et al., Mol Cell 2011
:
Rac1 regulates the activity of
mTORC1 and mTORC2 and controls cellular size
Li et al., Am J Physiol Cell Physiol 2011
(MAP Kinase Signaling System) :
Here, we demonstrate that the inhibition of mTORC1 by rapamycin (
mTORC1 inhibitor ), torin1 ( both mTORC1 and mTORC2 inhibitor ) or short hairpin RNA mediated knockdown of mTOR, regulatory associated protein of mTOR ( RAPTOR ), and
p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells
Fonseca et al., J Biol Chem 2011
:
Our data also reveal striking diversity in the
requirements for
MEK/ERK in the control of
mTORC1 between different cell types, pointing to additional signaling connections between phorbol esters and mTORC1, which do not involve MEK/ERK
Yecies et al., Cell Metab 2011
:
Therefore,
mTORC1 activation is not
sufficient to stimulate hepatic
SREBP1c in the absence of Akt signaling, revealing the existence of an additional downstream pathway also required for this induction
Wu et al., J Biol Chem 2011
:
The phosphorylation of
Raptor on these sites enhances mTORC1 activity, and
contributes largely to arsenite induced
mTORC1 activation
Yoshida et al., J Biol Chem 2011
:
Taken together, our results suggest that the
TSC complex
plays an important role in redox-sensitive
mTORC1 regulation and argues for the activation of mTORC1 in places other than the lysosome upon inhibition of the TSC complex
Jung et al., Autophagy 2011
:
These results demonstrate that
ULK1 negatively
regulates the kinase activity of
mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2
Kucejova et al., Mol Cancer Res 2011
(Carcinoma, Renal Cell) :
REDD1 induced
mTORC1 inhibition is dependent on a protein complex formed by the tuberous sclerosis complex (TSC)1 and 2 ( TSC2 ) proteins
Peña-Llopis et al., EMBO J 2011
(MAP Kinase Signaling System) :
V-ATPase regulation by
mTORC1 involves a transcription factor translocated in renal cancer, TFEB ...
mTORC1 coordinately
regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis
Shao et al., J Hepatol 2012
(Carcinoma, Hepatocellular...) :
The inhibition of both
mTORC1/2 not only efficiently
blocked mTORC1 signaling, but also abrogated AKT-feedback activation caused by selective mTORC1 inhibition
Magri et al., Cell stem cell 2011
(Epilepsy...) :
Notably,
mTORC1 dependent
Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs ... Notably,
mTORC1 dependent Akt inhibition and
STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs
Palazuelos et al., J Biol Chem 2012
:
Likewise,
CB(2) receptor engagement induced cell proliferation in an
mTORC1 dependent manner both in embryonic cortical slices and in adult hippocampal NPs
Vadysirisack et al., Methods Mol Biol 2012
:
Our work has demonstrated that the stress induced protein REDD1 is essential for hypoxia regulation of mTORC1 activity and has further defined the molecular mechanism whereby
REDD1 represses
mTORC1 activity under hypoxic stress
Willems et al., Leukemia 2012
(Leukemia, Myeloid, Acute) :
In addition, the
mTORC1 dependent
PI3K/Akt feedback activation was fully abrogated in AZD8055 treated AML cells ... In addition, the
mTORC1 dependent
PI3K/Akt feedback
activation was fully abrogated in AZD8055 treated AML cells
Magnuson et al., Biochem J 2012
:
mTORC1 ( mammalian TORC1 ) phosphorylates and
activates S6K1 and S6K2, whose first identified substrate was rpS6 ( ribosomal protein S6 ), a component of the 40S ribosome ...
mTORC1 ( mammalian TORC1 ) phosphorylates and
activates S6K1 and
S6K2 , whose first identified substrate was rpS6 ( ribosomal protein S6 ), a component of the 40S ribosome
Misra et al., J Cell Biochem 2012
(Prostatic Neoplasms) :
We further demonstrate that in 8-CPT-2Me-cAMP treated cells, Epac1 co-immunoprecipitates with AKAP, Raptor, Rictor, PDE3B, and PDE4D suggesting thereby that during
Epac1 induced activation of
mTORC1 and mTORC2, Epac1 may have an additional function as a `` scaffold '' protein
Sciarretta et al., Circulation 2012
(Metabolic Syndrome X...) :
Restoration of autophagy, through
Atg7 reexpression and
inhibition of
mTORC1 , increased cellular ATP content and reduced endoplasmic reticulum stress, thereby reducing CM death induced by Rheb activation
Settembre et al., EMBO J 2012
:
Conversely, pharmacological inhibition of
mTORC1 , as well as starvation and lysosomal disruption,
activates TFEB by promoting its nuclear translocation ... Interestingly, the
Rag GTPase complex, which senses lysosomal amino acids and
activates mTORC1 , is both necessary and sufficient to regulate starvation- and stress induced nuclear translocation of TFEB
Wu et al., J Biol Chem 2012
:
Although expression of the Raptor T908A mutant did not affect the mTORC1 integrity, it markedly impaired the
mTORC1 activation by insulin or by overexpression of the small
GTP binding protein RheB under nutrient starvation ... Although expression of the Raptor T908A mutant did not affect the mTORC1 integrity, it markedly impaired the
mTORC1 activation by
insulin or by overexpression of the small GTP binding protein RheB under nutrient starvation ... Our findings demonstrate an important
role for
ICK in modulating the activity of
mTORC1 through phosphorylation of Raptor Thr-908 and thus implicate a potential signaling mechanism by which ICK regulates cell proliferation and division
Ai et al., J Clin Invest 2012
(Hyperinsulinism...) :
Regulation of hepatic
LDL receptors by
mTORC1 and PCSK9 in mice
Melnik et al., World journal of diabetes 2012
:
High consumption of leucine-rich proteins explains exaggerated
mTORC1 dependent
insulin secretion, increased ß-cell growth and ß-cell proliferation promoting an early onset of replicative ß-cell senescence with subsequent ß-cell apoptosis
Zhao et al., Neoplasia (New York, N.Y.) 2012
(Neoplasms) :
Recently, we and others found that
DEPTOR , a naturally occurring
inhibitor of both
mTORC1 and mTORC2, was degraded by SCF ( Skp1-Cullin-F box proteins ) E3 ubiquitin ligase, the founding member of cullin-RING-ligases ( CRLs ), resulting in mTOR activation and cell proliferation
Durán et al., Mol Cell 2012
:
Thus,
mTORC1 senses and is
activated by
glutamine and leucine via glutaminolysis and a-ketoglutarate production upstream of Rag
Santini et al., J Biol Chem 2012
(MAP Kinase Signaling System...) :
These studies demonstrate that, in D1R expressing MSNs, l-DOPA induced activation of ERK and
mTORC1 requires
DARPP-32 and indicates the importance of the cAMP/DARPP-32 signaling cascade in dyskinesia
Yuan et al., J Biol Chem 2012
(Insulin Resistance) :
Lrictor ( KO ) mice also manifest defects in
insulin activated
mTORC1 activity, evidenced by decreased S6 kinase and Lipin1 phosphorylation
Urbanska et al., J Biol Chem 2012
:
We also identified
Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which
required mTORC1 and p70S6K1
Hall et al., Breast Cancer Res Treat 2012
(Breast Neoplasms) :
Previous studies have alternatively suggested that either
mTORC1 or mTORC2 is exclusively
required for
SGK1 's Ser422 phosphorylation and activation in breast cancer cells
Jung et al., J Toxicol Sci 2012
:
In conclusion, OA increases the proliferation and decreases the starvation induced apoptosis of SK-Hep1 cells via
mTORC1 activation
mediated by negative regulation of
AMPK
Laplante et al., Cell Metab 2012
(Obesity) :
DEPTOR activates the proadipogenic Akt/PKB-PPAR-? axis by dampening
mTORC1 mediated feedback inhibition of
insulin signaling
Kelleher et al., Am J Physiol Endocrinol Metab 2013
:
In conclusion, the results show an immobilization induced attenuation of
mTORC1 signaling
mediated by induction of
REDD1/2 and defective p70S6K1 phosphorylation
Ikeda et al., J Pharmacol Sci 2013
(Adrenal Gland Neoplasms...) :
Indeed, direct
mTORC1 inhibition
initiates ULK1/2 autophosphorylation and subsequent Atg13 and
FIP200 phosphorylation, inducing autophagy ... Indeed, direct
mTORC1 inhibition
initiates ULK1/2 autophosphorylation and subsequent
Atg13 and FIP200 phosphorylation, inducing autophagy
Regazzetti et al., PloS one 2012
(MAP Kinase Signaling System) :
In 3T3-L1 adipocytes, silencing of
REDD1 with siRNA
induces an increase of
mTORC1 activity as well as an inhibition of insulin signaling pathway and lipogenesis
Parrales et al., Cell Signal 2013
:
ERK1/2 dependent activation of
mTOR/mTORC1/p70S6K regulates thrombin induced RPE cell proliferation
Razmara et al., Cell communication and signaling : CCS 2013
:
Thus, whereas both
mTORC1 and mTORC2 are activated in a
PI3K dependent manner, different additional signaling pathways are needed
Martina et al., J Cell Biol 2013
:
Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to
mTORC1 dependent phosphorylation and inhibition of
TFEB
Wong et al., Biochem Biophys Res Commun 2013
:
Thus, we found that inhibiting
mTORC1 dependent
4E-BP1 phosphorylation mimics the effect of hypoxia on TXNIP expression
Matsui et al., EMBO Rep 2013
:
Knockdown of
Rab12 results in inhibition of autophagy and in increased activity of
mTORC1 ( mammalian/mechanistic target of rapamycin complex 1 ), an upstream regulator of autophagy
Jin et al., Cancer Lett 2013
(Lung Neoplasms) :
Herein, we show that the constitutive overexpression of
Redd1 , a negative
regulator of
mTORC1 , induces Akt activation in lung cancer cells
Melnik et al., Hautarzt 2013
(Acne Vulgaris...) :
mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is
activated by insulin,
IGF-1 and branched-chain essential amino acids, especially leucine ...
mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is
activated by insulin,
IGF-1 and branched-chain essential amino acids, especially leucine ...
mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is
activated by
insulin , IGF-1 and branched-chain essential amino acids, especially leucine
Bonito-Oliva et al., Neuropharmacology 2013
:
Haloperidol promotes
mTORC1 dependent phosphorylation of
ribosomal protein S6 via dopamine- and cAMP regulated phosphoprotein of 32 kDa and inhibition of protein phosphatase-1
Zeng et al., Nature 2013
(Inflammation) :
By contrast,
mTORC1 does not directly
affect the expression of
Foxp3 or anti- and pro-inflammatory cytokines in T ( reg ) cells, suggesting a non-conventional mechanism for T ( reg ) -cell functional regulation