mTOR Signaling in Growth Control and Disease

PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes

2003 • 8,996 citations

Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex

2005 • 5,837 citations

TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival

2003 • 3,731 citations

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

2006 • 3,685 citations

AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

2008 • 3,474 citations

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

2009 • 3,397 citations

Loss of autophagy in the central nervous system causes neurodegeneration in mice

2006 • 3,331 citations

Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

2005 • 3,088 citations

TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

2002 • 2,945 citations

mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery

2002 • 2,904 citations

TFEB Links Autophagy to Lysosomal Biogenesis

2011 • 2,814 citations

Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis

2007 • 2,597 citations

Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

2004 • 2,574 citations

Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB

2006 • 2,561 citations

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

2008 • 2,551 citations

Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease

2010 • 2,547 citations

Molecular mechanisms of mTOR-mediated translational control

2009 • 2,372 citations

Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids

2010 • 2,234 citations

Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive

2004 • 2,039 citations

Eaten alive: a history of macroautophagy

2010 • 1,971 citations

A mammalian protein targeted by G1-arresting rapamycin–receptor complex

1994 • 1,954 citations

Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy

2009 • 1,910 citations

Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1

2003 • 1,893 citations

ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery

2009 • 1,876 citations

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

2003 • 1,803 citations

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

2010 • 1,785 citations

Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action

2002 • 1,758 citations

An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1

2009 • 1,718 citations

The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress

2004 • 1,710 citations

A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

2012 • 1,685 citations

Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity

2004 • 1,631 citations

The roles of intracellular protein-degradation pathways in neurodegeneration

2006 • 1,579 citations

Identification of the Tuberous Sclerosis Complex-2 Tumor Suppressor Gene Product Tuberin as a Target of the Phosphoinositide 3-Kinase/Akt Pathway

2002 • 1,518 citations

mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H ⁺ -ATPase

2011 • 1,487 citations

RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs

1994 • 1,470 citations

Termination of autophagy and reformation of lysosomes regulated by mTOR

2010 • 1,441 citations

ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy

2009 • 1,421 citations

SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity

2006 • 1,365 citations

Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCα, but Not S6K1

2006 • 1,358 citations

mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex

2007 • 1,345 citations

Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism

1998 • 1,319 citations

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

2004 • 1,307 citations

TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth

2006 • 1,293 citations

Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells

2006 • 1,273 citations

Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

2005 • 1,272 citations

Regulation of TORC1 by Rag GTPases in nutrient response

2008 • 1,260 citations

HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression

2001 • 1,230 citations

Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway

2004 • 1,229 citations

Phosphorylation and Functional Inactivation of TSC2 by Erk

2005 • 1,229 citations

SREBP Activity Is Regulated by mTORC1 and Contributes to Akt-Dependent Cell Growth

2008 • 1,222 citations

p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling

2008 • 1,221 citations

Hypothalamic mTOR Signaling Regulates Food Intake

2006 • 1,217 citations

The coordinate regulation of the p53 and mTOR pathways in cells

2005 • 1,199 citations

PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase

2007 • 1,176 citations

Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

2003 • 1,160 citations

DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival

2009 • 1,151 citations

Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin

2002 • 1,147 citations

RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1

1998 • 1,136 citations

Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40

2007 • 1,132 citations

The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

2004 • 1,101 citations

Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity

2012 • 1,089 citations

mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway

2011 • 1,082 citations

Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

2009 • 1,064 citations

The mTOR-Regulated Phosphoproteome Reveals a Mechanism of mTORC1-Mediated Inhibition of Growth Factor Signaling

2011 • 1,040 citations

Influence of TOR kinase on lifespan in C. elegans

2003 • 1,017 citations

Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling

2001 • 1,012 citations

Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

2001 • 981 citations

Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster

2010 • 974 citations

Phosphorylation of the Translational Repressor PHAS-I by the Mammalian Target of Rapamycin

1997 • 953 citations

Akt regulates growth by directly phosphorylating Tsc2

2002 • 932 citations

GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR

2003 • 927 citations

Selective versus Total Insulin Resistance: A Pathogenic Paradox

2008 • 888 citations

Regulation of PTEN Transcription by p53

2001 • 887 citations

mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

2008 • 876 citations

Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells

1995 • 859 citations

Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans

2006 • 856 citations

Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice

2010 • 849 citations

Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression

1993 • 832 citations

Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate That Negatively Regulates Insulin Signaling

2011 • 818 citations

Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase

2005 • 744 citations

AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity

2009 • 741 citations

Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase

2004 • 737 citations

A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans

2008 • 724 citations

Control of p70 S6 kinase by kinase activity of FRAP in vivo

1995 • 717 citations

mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs

2010 • 687 citations

Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis

2010 • 674 citations

mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s

2006 • 668 citations

Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling

2008 • 660 citations

Phosphorylation of Ribosomal Protein S6 Is Inhibitory for Autophagy in Isolated Rat Hepatocytes

1995 • 654 citations

With TOR, Less Is More: A Key Role for the Conserved Nutrient-Sensing TOR Pathway in Aging

2010 • 629 citations

Activation of mTORC2 by Association with the Ribosome

2011 • 625 citations

mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells

2009 • 619 citations

IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

2007 • 619 citations

Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy

2008 • 614 citations

A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle

2005 • 612 citations

mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells

2004 • 606 citations

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

2010 • 597 citations

Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer

2005 • 596 citations

An Emerging Role of mTOR in Lipid Biosynthesis

2009 • 579 citations

Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways

2011 • 561 citations

Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans

2009 • 551 citations

Insulin Resistance Accelerates Muscle Protein Degradation: Activation of the Ubiquitin-Proteasome Pathway by Defects in Muscle Cell Signaling

2006 • 546 citations

Increased Activation of the Mammalian Target of Rapamycin Pathway in Liver and Skeletal Muscle of Obese Rats: Possible Involvement in Obesity-Linked Insulin Resistance

2004 • 536 citations

4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila

2009 • 523 citations

TSC2 regulates VEGF through mTOR-dependent and -independent pathways

2003 • 521 citations

Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity

2006 • 497 citations

mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability

2004 • 471 citations

Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration

2008 • 468 citations

PRAS40 Regulates mTORC1 Kinase Activity by Functioning as a Direct Inhibitor of Substrate Binding

2007 • 465 citations

Disruption of the Mouse mTOR Gene Leads to Early Postimplantation Lethality and Prohibits Embryonic Stem Cell Development

2004 • 464 citations

Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

2009 • 454 citations

Genetic Dissection of the Oncogenic mTOR Pathway Reveals Druggable Addiction to Translational Control via 4EBP-eIF4E

2010 • 451 citations

Hypoinsulinaemia, glucose intolerance and diminished β-cell size in S6K1-deficient mice

2000 • 448 citations

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

2007 • 446 citations

Identification of Protor as a novel Rictor-binding component of mTOR complex-2

2007 • 436 citations

Regulation of TFEB and V-ATPases by mTORC1

2011 • 434 citations

Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

2004 • 431 citations

Loss of the Tuberous Sclerosis Complex Tumor Suppressors Triggers the Unfolded Protein Response to Regulate Insulin Signaling and Apoptosis

2008 • 425 citations

Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin

2006 • 420 citations

Chronic Rapamycin Treatment Causes Glucose Intolerance and Hyperlipidemia by Upregulating Hepatic Gluconeogenesis and Impairing Lipid Deposition in Adipose Tissue

2010 • 416 citations

Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

2011 • 400 citations

Longevity pathways converge on autophagy genes to regulate life span inCaenorhabditis elegans

2008 • 399 citations

Nutrients Suppress Phosphatidylinositol 3-Kinase/Akt Signaling via Raptor-Dependent mTOR-Mediated Insulin Receptor Substrate 1 Phosphorylation

2005 • 395 citations

4E-BP1 Is a Key Effector of the Oncogenic Activation of the AKT and ERK Signaling Pathways that Integrates Their Function in Tumors

2010 • 390 citations

Structure of the Human mTOR Complex I and Its Implications for Rapamycin Inhibition

2010 • 385 citations

Multiallelic Disruption of the rictor Gene in Mice Reveals that mTOR Complex 2 Is Essential for Fetal Growth and Viability

2006 • 384 citations

mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice

2009 • 379 citations

Insulin Stimulates Adipogenesis through the Akt-TSC2-mTORC1 Pathway

2009 • 377 citations

mTOR Inhibition by Rapamycin Prevents β-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes

2008 • 364 citations

mTOR Mediates Wnt-Induced Epidermal Stem Cell Exhaustion and Aging

2009 • 357 citations

The Tuberous Sclerosis Protein TSC2 Is Not Required for the Regulation of the Mammalian Target of Rapamycin by Amino Acids and Certain Cellular Stresses

2005 • 357 citations

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR

2007 • 353 citations

Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor

2010 • 336 citations

Biochemical, Cellular, and In vivo Activity of Novel ATP-Competitive and Selective Inhibitors of the Mammalian Target of Rapamycin

2009 • 323 citations

Regulation of mTORC1 and mTORC2 Complex Assembly by Phosphatidic Acid: Competition with Rapamycin

2008 • 322 citations

Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2

2007 • 316 citations

MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae

2007 • 301 citations

Amino Acid-Induced Translation of TOP mRNAs Is Fully Dependent on Phosphatidylinositol 3-Kinase-Mediated Signaling, Is Partially Inhibited by Rapamycin, and Is Independent of S6K1 and rpS6 Phosphorylation

2001 • 296 citations

The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila

2004 • 294 citations

Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells

2009 • 293 citations

PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis

2007 • 292 citations

The Role of Adipose Tissue and Lipotoxicity in the Pathogenesis of Type 2 Diabetes

2010 • 289 citations

Dominant Missense Mutations in a Novel Yeast Protein related to Mammalian Phosphatidylinositol 3-Kinase and VPS34 Abrogate Rapamycin Cytotoxicity

1993 • 271 citations

A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling

2007 • 253 citations

Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)

2010 • 251 citations

mTORC2 Activity Is Elevated in Gliomas and Promotes Growth and Cell Motility via Overexpression of Rictor

2007 • 248 citations

Fat Cell–Specific Ablation of Rictor in Mice Impairs Insulin-Regulated Fat Cell and Whole-Body Glucose and Lipid Metabolism

2010 • 244 citations

Tti1 and Tel2 Are Critical Factors in Mammalian Target of Rapamycin Complex Assembly

2010 • 241 citations

mTORC2 Regulates Neutrophil Chemotaxis in a cAMP- and RhoA-Dependent Fashion

2010 • 212 citations

Muscle-Specific Deletion of Rictor Impairs Insulin-Stimulated Glucose Transport and Enhances Basal Glycogen Synthase Activity

2007 • 207 citations

Beyond Rapalog Therapy: Preclinical Pharmacology and Antitumor Activity of WYE-125132, an ATP-Competitive and Specific Inhibitor of mTORC1 and mTORC2

2010 • 206 citations

mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1

2010 • 202 citations

Phosphatidic acid signaling to mTOR: Signals for the survival of human cancer cells

2009 • 201 citations

Disruption of Tsc2 in pancreatic β cells induces β cell mass expansion and improved glucose tolerance in a TORC1-dependent manner

2008 • 192 citations

S6K1 Plays a Critical Role in Early Adipocyte Differentiation

2010 • 186 citations

The Role of Hypothalamic Mammalian Target of Rapamycin Complex 1 Signaling in Diet-Induced Obesity

2008 • 184 citations

Mediobasal Hypothalamic p70 S6 Kinase 1 Modulates the Control of Energy Homeostasis

2008 • 184 citations

Requirement of the mTOR Kinase for the Regulation of Maf1 Phosphorylation and Control of RNA Polymerase III-dependent Transcription in Cancer Cells

2010 • 175 citations

Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney

2011 • 175 citations

Biphasic Response of Pancreatic β-Cell Mass to Ablation of Tuberous Sclerosis Complex 2 in Mice

2008 • 170 citations

DAP1, a Novel Substrate of mTOR, Negatively Regulates Autophagy

2010 • 159 citations

Small molecule enhancers of autophagy for neurodegenerative diseases

2008 • 154 citations

Rictor/mTORC2 Is Essential for Maintaining a Balance Between β-Cell Proliferation and Cell Size

2011 • 152 citations

Amino Acid Signaling to mTOR Mediated by Inositol Polyphosphate Multikinase

2011 • 140 citations

Pushing the Envelope in the mTOR Pathway: The Second Generation of Inhibitors

2011 • 131 citations

Management of Side Effects of Sirolimus Therapy

2009 • 125 citations

PP2AT61ɛ Is an Inhibitor of MAP4K3 in Nutrient Signaling to mTOR

2010 • 122 citations

Rapamycin Inhibits Polyglutamine Aggregation Independently of Autophagy by Reducing Protein Synthesis

2008 • 122 citations

Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1

2010 • 118 citations

The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile

2011 • 104 citations

Reduced VEGF Production, Angiogenesis, and Vascular Regrowth Contribute to the Antitumor Properties of Dual mTORC1/mTORC2 Inhibitors

2011 • 90 citations

Rapamycin‐sensitive phase of 3T3‐L1 preadipocyte differentiation after clonal expansion

2001 • 80 citations

Role of S6K1 in regulation of SREBP1c expression in the liver

2011 • 72 citations

Decreased IRS Signaling Impairs β-Cell Cycle Progression and Survival in Transgenic Mice Overexpressing S6K in β-Cells

2010 • 64 citations

TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells

2008 • 63 citations

MAP4K3 regulates body size and metabolism in Drosophila

2010 • 62 citations

HER2が増幅されPI3K3CAが変異した乳癌細胞におけるPI3K/mTor二重阻害剤NVP‐BEZ235による特異的アポトーシス誘発

2009 • 60 citations

Rapamycin, an mTOR inhibitor, disrupts triglyceride metabolism in guinea pigs

2006 • 51 citations

Mammalian target of rapamycin complex 1 (mTORC1) signaling in energy balance and obesity

2009 • 29 citations