The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions. The map complies with both the systems biology markup language (SBML) and graphical notation (SBGN) for computational analysis and graphical representation, respectively. As captured in the mTOR map, we review and discuss our current understanding of the mTOR signaling network and highlight the impact of mTOR feedback and crosstalk regulations on drug-based cancer therapy. This map is available on the Payao platform, a Web 2.0 based community-wide interactive process for creating more accurate and information-rich databases. Thus, this comprehensive map of the mTOR network will serve as a tool to facilitate systems-level study of up-to-date mTOR network components and signaling events toward the discovery of novel regulatory processes and therapeutic strategies for cancer.
Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle
RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation
Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin.
The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models
The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors
The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses.
Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase
Identification of FIP200 interaction with the TSC1-TSC2 complex and its role in regulation of cell size control
TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth
SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
Inhibition of mammalian target of rapamycin signaling by CCI-779 (temsirolimus) induces growth inhibition and cell cycle arrest in Cashmere goat fetal fibroblasts (Capra hircus).
Rapamycin induces Bad phosphorylation in association with its resistance to human lung cancer cells.
BiNoM 2.0, a Cytoscape plugin for accessing and analyzing pathways using standard systems biology formats
PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy
Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice.
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome
Crosstalk between Edc4 and mammalian target of rapamycin complex 1 (mTORC1) signaling in mRNA decapping
Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice
A high leucine diet mitigates cardiac injury and improves survival after acute myocardial infarction
mTOR expression and prognosis in elderly patients with laryngeal carcinoma: uni- and multivariate analyses
An integrative model links multiple inputs and signaling pathways to the onset of DNA synthesis in hepatocytes.
A modelling-experimental approach reveals insulin receptor substrate (IRS)-dependent regulation of adenosine monosphosphate-dependent kinase (AMPK) by insulin
Systems-based understanding of pharmacological responses with combinations of multidisciplinary methodologies
Complex regulation of autophagy in cancer - integrated approaches to discover the networks that hold a double-edged sword
Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps
Critical role of SCD1 in autophagy regulation via lipogenesis and lipid rafts-coupled AKT-FOXO1 signaling pathway
Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review
Cancer Genomics (Keystone)
Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.