Protein kinase mtor. Medical search. Frequent questions

To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. (nih.gov)
EGFR Tyrosine Kinase Inhibitor (PD153035) Improves Glucose Tolerance and Insulin Action in High-Fat Diet-Fed Mice. (diabetesjournals.org)
To date, all of the kinase inhibitor drugs on the market are for use in an oncology setting. (soci.org)
Reversible and selective inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) (IC50 values are 0.28 and 5.3 μM respectively). (fishersci.com)
A protein kinase inhibitor of the m ammalian t arget o f r apamycin (mTOR), a protein that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis and transcription. (ebi.ac.uk)
p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
LDN193189 hydrochloride has been used as an ALK2/3 (type I receptor serine-threonine kinases) inhibitor, to study the effect of TGFβ1/2/3 (tumor growth factor β) and BMP (bone morphogenetic protein) signaling on spinal cord development in zebrafish. (sigmaaldrich.com)
Rapamycin-derivative kinase inhibitor. (medscape.com)

A Central Role for Neuronal AMP-Activated Protein Kinase (AMPK) and Mammalian Target of Rapamycin (mTOR) in High-Protein Diet-Induced Weight Loss. (diabetesjournals.org)
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene. (wikipedia.org)
That of FKBP12-rapamycin remained mysterious until genetic and molecular studies in yeast established FKBP12 as the target of rapamycin, and implicated TOR1 and TOR2 as the targets of FKBP12-rapamycin in 1991 and 1993, followed by studies in 1994 when several groups, working independently, discovered the mTOR kinase as its direct target in mammalian tissues. (wikipedia.org)
Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. (nih.gov)
Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. (frontiersin.org)
This complex inhibits mammalian target of rapamycin (mTOR) kinase, a key protein in cells that regulate the gene translation responsible for cell-cycle regulation. (medscape.com)
Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. (benthamscience.com)
Malik AR, Urbanska M, Skalecka A, Jaworski J. Beyond control of protein translation: what we have learned about the non-canonical regulation and function of mammalian target of rapamycin (mTOR). (benthamscience.com)
In vitro analysis reveals that LDN193189 inhibits a number of intracellular kinases such as, mitogen activated protein kinase 14 and 8 ( p38and c-Jun N -terminal kinase respectively), as well as those associated with AKT (serine/threonine kinase) and mTOR (mammalian target of rapamycin) signaling mechanisms. (sigmaaldrich.com)

AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK has been demonstrated to mediate, at least in part, the effects of a number of physiological and pharmacological factors that exert beneficial effects on these disorders. (aspetjournals.org)
Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells. (nih.gov)
Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. (jci.org)
Another important pathway is the AMP-activated protein kinase (AMPK) pathway. (sigmaaldrich.com)
AMPK is often considered a metabolic checkpoint as it can control cell proliferation when activated under energetic stress, and activation of AMKP results in the inhibition of mTOR activity. (sigmaaldrich.com)
In addition, these 3 essential oils modulated the activity of the AMPK/mTOR signaling pathway. (spandidos-publications.com)
In conclusion, the present study indicated that frankincense, pine needle and geranium essential oils were involved in the progression of BC cells possibly through the AMPK/mTOR pathway. (spandidos-publications.com)
Moreover, we elucidated the regulatory AMPK/mTOR pathway involving essential oils in BC cell proliferation, invasion and apoptosis development. (spandidos-publications.com)
AMPK pathways inhibit biosynthetic pathways with energy consumption, such as protein, fatty acid and glycogen synthesis. (springer.com)
These complexes interact with 5'-AMP-activated protein kinase (AMPK) that is part of the mechanistic target of rapamycin (mTOR) pathway, which is involved in cellular energy, cytokinesis, cell motility, cellular adhesion, and nutrient sensing. (medscape.com)

Further studies showed that UASR1 activated AKT and AKT-mediated mTOR signaling pathway to stimulate cell proliferation and growth. (jcancer.org)
Taken together, our data suggest that UASR1 plays an oncogenic role in breast cancer cells through activation of the AKT/mTOR signaling pathway, being a novel RNA oncogene. (jcancer.org)
Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator α (CREM-α) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation. (jci.org)
Understanding the mTOR signaling pathway via mathematical modeling. (crossref.org)
Metformin generates a mild and transient inhibition of the mTOR pathway, suggesting that ongoing therapy would be needed for best effects. (naturalmedicinejournal.com)
Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. (rcsb.org)
The PI3K pathway is considered to be a major determinant of the glycolytic phenotype through AKT1 and mTOR signaling, and subsequent downstream Hypoxy Inducible Factor 1 (HIF-1) transcription factor activation. (sigmaaldrich.com)
The pathway, which involves a protein kinase called mTOR, stimulates the transport of a glucose-importing protein called GLUT1 to the surface of brown fat cells. (medicalxpress.com)
The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. (aging-us.com)
Oncogenic Ras induces the constitutive activation of Ras/Raf/MEK/ERK signaling pathway, which, in turn, activates other effector pathways, in particular, PI3K-mTOR signaling [ 17 ]. (aging-us.com)
Reduces cell proliferation and angiogenesis by inhibition of mTOR pathway. (medscape.com)
In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation. (bvsalud.org)

Intracellular signalling pathways: covering the major pathways in cells (MAPK, PI3K-AKT, mTOR, JAK-STAT, SMAD, IKK-NF- k B, Wnt), their components and key roles of protein kinases and phosphatases. (manchester.ac.uk)
In paper I, we identified and tested novel inhibitors targeting the PIM, PI3K, and mTOR pathways. (lu.se)

Mechanistic target of rapamycin (mTOR) kinase functions in two multiprotein complexes: lysosomal mTOR complex 1 (mTORC1) and mTORC2 at the plasma membrane. (nature.com)
Sequence analysis of mTOR revealed it to be the direct ortholog of proteins encoded by the yeast target of rapamycin 1 and 2 (TOR1 and TOR2) genes, which Joseph Heitman, Rao Movva, and Michael N. Hall had identified in August 1991 and May 1993. (wikipedia.org)
An adaptor protein, consisting of seven WD REPEATS along its length, that functions as a component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 and MTORC2 COMPLEX. (bvsalud.org)

Which medications in the drug class Antineoplastic Agents, mTOR Kinase Inhibitors are used in the treatment of Non-Hodgkin Lymphoma (NHL)? (medscape.com)
They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
In a keynote lecture, Professor Malcolm Ranson (University of Manchester / Christie Hospital) provided an insight into the clinical aspects of developing kinase inhibitors as effective medicines. (soci.org)
Vertex described its progress on inhibition of Flt-3, AstraZeneca presented on mTor inhibitors and Boehringer Ingelheim discussed its programme on Plk1 inhibitors. (soci.org)
Additional presentations detailed kinase inhibitors, which have potential for the treatment of diseases in therapeutic areas other than cancer. (soci.org)
mTOR inhibitors are used to prevent transplant rejection and in treatment of cancer. (ebi.ac.uk)
Treatment includes plasma exchange as needed for hyperviscosity and systemic therapy with alkylating drugs, corticosteroids, nucleoside analogs, Bruton's tyrosine kinase (BTK) inhibitors, venetoclax , or monoclonal antibodies. (msdmanuals.com)

In 1994, researchers working in the labs of Stuart L. Schreiber, Solomon H. Snyder and Robert T. Abraham independently discovered a protein that directly interacts with FKBP12-rapamycin, which became known as mTOR due to its homology to the yeast TOR/DRR genes. (wikipedia.org)
The two natural products were used to discover the FK506- and rapamycin-binding proteins, including FKBP12, and to provide evidence that FKBP12-FK506 and FKBP12-rapamycin might act through gain-of-function mechanisms that target distinct cellular functions. (wikipedia.org)
Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. (aacrjournals.org)

TGF-β-activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. (jci.org)
Akt pathways have effects on apoptosis, protein synthesis, metabolism and cell cycle. (springer.com)

We demonstrate that protein kinase N (PKN) facilitates mTORC1 signalling by repressing PI3KC2-β-mediated phosphatidylinositol-3,4-bisphosphate synthesis downstream of mTORC2. (nature.com)
mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. (wikipedia.org)

Kanekiyo T, Bu G. The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer's disease. (benthamscience.com)
Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)
The targets of the epilepsy pipeline drugs market are Gamma-Aminobutyric Acid Type A Receptor Subunit (GABA, Voltage Gated Sodium Channel, Cannabinoid Receptor 2, Cannabinoid Receptor 1, Potassium Voltage Gated Channel Subfamily KQT Member 2, Potassium Voltage Gated Channel Subfamily KQT Member 3, Sodium Channel Protein Type 8 Subunit Alpha, Sodium Channel Protein Type 1 Subunit Alpha, 5-Hydroxytryptamine Receptor, and Serine/Threonine Protein Kinase mTOR. (globaldata.com)

Fig. 5: mTORC2 signalling triggers PKN2 activation to control PI3KC2-β phosphorylation and sequestration with 14-3-3 proteins. (nature.com)
As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. (wikipedia.org)

We also examined the effects of FLX on the expression of extracellular signal-regulated kinase (ERK) 1/2-related signaling within the ventral tegmental area (VTA) of adolescent mice and Sprague Dawley rats. (jneurosci.org)

It interacts directly with MTOR to enhance its kinase activity and stabilizes the MTOR-RPTOR PROTEIN interaction in nutrient-poor conditions, favoring RPTOR inhibition of MTOR activity. (bvsalud.org)

The SMAD proteins are a family of transcription factors consisting of 8 members, SMAD1-8, which are further subdivided into 3 classes based on structural and functional properties. (shu.edu)
It has also been used to inhibit SMAD (homologues of the Drosophila protein, mothers against decapentaplegic), in order to prevent non neuronal differentiation. (sigmaaldrich.com)

Immunosuppressant, which forms an inhibitory complex with the immunophilin FKBP12, which binds to and inhibits the ability of mTOR to phosphorylate downstream substrates such as the S6Ks and 4EBPs. (medscape.com)

Fig. 1: Serum mitogen-induced phosphorylation of PI3KC2-β induces complex formation with 14-3-3 proteins. (nature.com)
This complex behavioral profile was accompanied by decreases in ERK2 mRNA and protein phosphorylation within the VTA, while stress alone resulted in opposite neurobiological effects. (jneurosci.org)
The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
Introduction to cell signalling: signalling networks, protein-protein interactions, protein phosphorylation/de-phosphorylation. (manchester.ac.uk)

Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. (jci.org)

The serine/threonine kinase protein kinase D1 (PKD1) is a stress-responsive kinase and sensor for reactive oxygen species, which can initiate cell survival through NF-κB signaling. (biologists.com)

To date, it is well known that lncRNAs participate in chromatin modifications and transcriptional and translational regulation of protein-encoding genes or regulate protein function and activity through specific binding [ 3 - 5 ]. (jcancer.org)

The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. (cancerindex.org)

Starvation-induced MTOR inactivation and PPP3/calcineurin activation were shown to promote the nuclear translocation of TFEB. (bvsalud.org)

Only 1.5% of nucleic acids in human genome are used for protein encoding, but other 98.5% of the genome does not encode proteins. (jcancer.org)
The members of this family encode proteins with 50 to 80% sequence identity to each other. (nih.gov)

mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. (wikipedia.org)

Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the apoptosis signal-regulating kinase (ASK1) signaling cascade. (benthamscience.com)

Representative gel showing phosphorylated MKK6 protein in in vitro kinase assay (KA) in plantaris muscle. (jci.org)
Moreover, we further confirmed that both RNA and protein level of RPSA increased upon inflammatory stimulation in vitro. (bvsalud.org)

Recent technological advances are now helping to refine the mitochondrial proteome and are assisting in characterizing mitochondrial protein functions, paving the way for better diagnosis and treatment of mitochondrial diseases. (nature.com)

Active PKN2 phosphorylates PI3KC2-β to trigger PI3KC2-β complex formation with inhibitory 14-3-3 proteins. (nature.com)

In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells. (cancerindex.org)
Cells have a protein on their surface called PD-1 (in orange above). (shu.edu)
Macroglobulinemia is a malignant plasma cell disorder in which B cells produce excessive amounts of IgM M-proteins. (msdmanuals.com)

Consequently, the regulation/ misregulation of kinases has linked them to a number of diseases and they provide a wealth of opportunity as targets for drug discovery. (soci.org)

Fig. 2: PKN2 facilitates mTORC1 activation by phosphorylating PI3KC2-β and triggering sequestration by 14-3-3 proteins. (nature.com)

Scope includes mutations and abnormal protein expression. (cancerindex.org)

Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)

G ) Representative immunoblots of phosphorylated and total Akt, mTOR, and 4E-BP1 protein levels and unrelated protein GAPDH in plantaris muscle of Tak1 fl/fl and Tak1 mKO mice. (jci.org)

Some of these proteins are antibodies directed toward autologous IgG (rheumatoid factors) or I antigens (cold agglutinins). (msdmanuals.com)

Raw data for results from screening kinase activity towards T279 of PI3KC2-β are provided in Supplementary Table 2 . (nature.com)
B ) Densitometry quantification of TAK1 enzymatic activity and phosphorylated vs. total levels of TAK1 and mTOR in plantaris muscle of Tak1 fl/fl and Tak1 mKO mice. (jci.org)

Protein-protein interaction (PPI) network was generated at STRING database, and hub genes were identified by the Cytoscape software. (bvsalud.org)

mTOR also reduces the cell growth factors (eg, vascular endothelial growth factor) involved in new blood vessel development. (medscape.com)

However, it is unknown if mTOR inhibition affects aging or its consequences in humans. (nih.gov)

Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. (jci.org)
Study biologically important molecules including DNA, RNA and proteins, as well as the molecular events that govern cell function. (manchester.ac.uk)

Autophagy represents a caspase-independent process characterized by accumulation of autophagosomes in the cytoplasm and their subsequent fusion with lysosomes for degradation of unused or misfolded proteins or damaged structures such as ribosomes (ribophagy) and mitochondria (mitophagy). (aging-us.com)

Anatomy16

Organisms9

Chemicals and Drugs173

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes40

Disciplines and Occupations1

Information Science3

Inhibitor9

Mammalian11

AMPK10

Pathway12

PI3K2

Target of rapamycin3

Inhibitors8

Rapamycin3

Pathways2

Phosphatidylinositol2

Receptor3

MTORC22

Extracellular signal1

Inhibition of mTOR1

SMAD2

Downstream1

Phosphorylation4

Inhibits1

Reactive oxygen1

Transcriptional1

Transcription1

Inactivation1

Encode proteins2

Regulate1

Apoptosis1

Vitro2

Mitochondrial1

Complex1

Cells4

Regulation1

Activation1

Mutations1

Synthesis1

GAPDH1

Antibodies1

Activity2

Interaction1

Reduces1

Humans1

Cell2

Autophagy1