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Citations to this article

Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
Hongbing Zhang, … , Christopher L. Carpenter, David J. Kwiatkowski
Hongbing Zhang, … , Christopher L. Carpenter, David J. Kwiatkowski
Published October 15, 2003
Citation Information: J Clin Invest. 2003;112(8):1223-1233. https://doi.org/10.1172/JCI17222.
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Article Oncology

Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR

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Abstract

Tuberous sclerosis (TSC) is a familial tumor syndrome due to mutations in TSC1 or TSC2, in which progression to malignancy is rare. Primary Tsc2–/– murine embryo fibroblast cultures display early senescence with overexpression of p21CIP1/WAF1 that is rescued by loss of TP53. Tsc2–/–TP53–/– cells, as well as tumors from Tsc2+/– mice, display an mTOR-activation signature with constitutive activation of S6K, which is reverted by treatment with rapamycin. Rapamycin also reverts a growth advantage of Tsc2–/–TP53–/– cells. Tsc1/Tsc2 does not bind directly to mTOR, however, nor does it directly influence mTOR kinase activity or cellular phosphatase activity. There is a marked reduction in Akt activation in Tsc2–/–TP53–/– and Tsc1–/– cells in response to serum and PDGF, along with a reduction in cell ruffling. PDGFRα and PDGFRβ expression is markedly reduced in both the cell lines and Tsc mouse renal cystadenomas, and ectopic expression of PDGFRβ in Tsc2-null cells restores Akt phosphorylation in response to serum, PDGF, EGF, and insulin. This activation of mTOR along with downregulation of PDGFR PI3K-Akt signaling in cells lacking Tsc1 or Tsc2 may explain why these genes are rarely involved in human cancer. This is in contrast to PTEN, which is a negative upstream regulator of this pathway.

Authors

Hongbing Zhang, Gregor Cicchetti, Hiroaki Onda, Henry B. Koon, Kirsten Asrican, Natalia Bajraszewski, Francisca Vazquez, Christopher L. Carpenter, David J. Kwiatkowski

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Autophagy 2018
Neural progenitors derived from Tuberous Sclerosis Complex patients exhibit attenuated PI3K/AKT signaling and delayed neuronal differentiation
AJ Zucco, VD Pozzo, A Afinogenova, RP Hart, O Devinsky, G D'Arcangelo
Molecular and cellular neurosciences 2018
Genome-wide CRISPR-KO Screen Uncovers mTORC1-Mediated Gsk3 Regulation in Naive Pluripotency Maintenance and Dissolution
M Li, JS Yu, K Tilgner, SH Ong, H Koike-Yusa, K Yusa
Cell Reports 2018
mTOR signaling regulates central and peripheral circadian clock function
C Ramanathan, ND Kathale, D Liu, C Lee, DA Freeman, JB Hogenesch, R Cao, AC Liu, A Kramer
PLoS genetics 2018
An integrated approach to infer cross-talks between intracellular protein transport and signaling pathways
KP Tripathi, M Piccirillo, MR Guarracino
BMC bioinformatics 2018
Roles for neuronal and glial autophagy in synaptic pruning during development
OJ Lieberman, AF McGuirt, G Tang, D Sulzer
Neurobiology of Disease 2018
Vps34-mediated macropinocytosis in Tuberous Sclerosis Complex 2-deficient cells supports tumorigenesis
H Filippakis, A Belaid, B Siroky, C Wu, N Alesi, T Hougard, J Nijmeh, HC Lam, EP Henske
Scientific Reports 2018
Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery
HJ Hsieh, W Zhang, SH Lin, WH Yang, JZ Wang, J Shen, Y Zhang, Y Lu, H Wang, J Yu, GB Mills, G Peng
Nature Communications 2018
Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir-bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death.
Johnson CE, Dunlop EA, Seifan S, McCann HD, Hay T, Parfitt GJ, Jones AT, Giles PJ, Shen MH, Sampson JR, Errington RJ, Davies DM, Tee AR
Oncogene 2018
mTORC1 Loss Impairs Epidermal Adhesion via TGF-β/Rho Kinase Activation
Kaushal Asrani, Akshay Sood, Alba Torres, Dan Georgess, Pornima Phatak, Harsimar Kaur, Amber Dubin, C. Conover Talbot Jr., Loubna Elhelu, Andrew Ewald, Bo Xiao, Paul Worley, Tamara Lotan
Journal of Clinical Investigation 2017
Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors
V Stepanova, KV Dergilev, KR Holman, YV Parfyonova, ZI Tsokolaeva, M Teter, EN Atochina-Vasserman, A Volgina, SV Zaitsev, SP Lewis, FG Zabozlaev, K Obraztsova, VP Krymskaya, DB Cines
The Journal of biological chemistry 2017
Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity
S Faes, N Demartines, O Dormond
Oxidative medicine and cellular longevity 2017
Hyperactivated mTORC1 downregulation of FOXO3a/PDGFRα/AKT cascade restrains tuberous sclerosis complex-associated tumor development
L Wang, Z Ni, Y Liu, S Ji, F Jin, K Jiang, J Ma, C Ren, H Zhang, Z Hu, X Zha
Oncotarget 2017
Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling
G Lee, Y Zheng, S Cho, C Jang, C England, JM Dempsey, Y Yu, X Liu, L He, PM Cavaliere, A Chavez, E Zhang, M Isik, A Couvillon, NE Dephoure, TK Blackwell, JJ Yu, JD Rabinowitz, LC Cantley, J Blenis
Cell 2017
A screening strategy for the discovery of drugs that reduce C/EBPβ-LIP translation with potential calorie restriction mimetic properties
MA Zaini, C Müller, T Ackermann, J Reinshagen, G Kortman, O Pless, CF Calkhoven
Scientific Reports 2017
Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing
B Carroll, G Nelson, Y Rabanal-Ruiz, O Kucheryavenko, NA Dunhill-Turner, CC Chesterman, Q Zahari, T Zhang, SE Conduit, CA Mitchell, OD Maddocks, P Lovat, T Zglinicki, VI Korolchuk
The Journal of Cell Biology 2017
Glucosyltransferase Activity of Clostridium difficile Toxin B Triggers Autophagy-mediated Cell Growth Arrest
R He, J Peng, P Yuan, J Yang, X Wu, Y Wang, W Wei
Scientific Reports 2017
Heterozygous loss of TSC2 alters p53 signaling and human stem cell reprogramming
LC Armstrong, G Westlake, JP Snow, B Cawthon, E Armour, AB Bowman, KC Ess
Human Molecular Genetics 2017
Osteopontin is Critical for Hyperactive mTOR-Induced Tumorigenesis in Oral Squamous Cell Carcinoma
N Gan, S Zou, W Hang, D Yang, X Zhang, Y Yin
Journal of Cancer 2017
Combined Targeting of mTOR and Akt Using Rapamycin and MK-2206 in The Treatment of Tuberous Sclerosis Complex
S Ji, W Lin, L Wang, Z Ni, F Jin, X Zha, G Fei
Journal of Cancer 2017
Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia
JS Lim, R Gopalappa, SH Kim, S Ramakrishna, M Lee, W Kim, J Kim, SM Park, J Lee, JH Oh, HD Kim, CH Park, JS Lee, S Kim, DS Kim, JM Han, HC Kang, HH Kim, JH Lee
The American Journal of Human Genetics 2017
mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability
AJ Valvezan, M Turner, A Belaid, HC Lam, SK Miller, MC McNamara, C Baglini, BE Housden, N Perrimon, DJ Kwiatkowski, JM Asara, EP Henske, BD Manning
Cancer Cell 2017
ZRF1 is a novel S6 kinase substrate that drives the senescence programme
M Barilari, G Bonfils, C Treins, V Koka, DD Villeneuve, S Fabrega, M Pende
The EMBO Journal 2017
Targeting protein homeostasis with nelfinavir/salinomycin dual therapy effectively induces death of mTORC1 hyperactive cells
EA Dunlop, CE Johnson, M Wiltshire, RJ Errington, AR Tee
Oncotarget 2017
Evidence of renal angiomyolipoma neoplastic stem cells arising from renal epithelial cells
AF Gonçalves, M Adlesic, S Brandt, T Hejhal, S Harlander, L Sommer, O Shakhova, PJ Wild, IJ Frew
Nature Communications 2017
mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci
I Kelsey, M Zbinden, V Byles, M Torrence, BD Manning
Scientific Reports 2017
MTORC1 Regulates both General Autophagy and Mitophagy Induction after Oxidative Phosphorylation Uncoupling
A Bartolomé, A García-Aguilar, SI Asahara, Y Kido, C Guillén, UB Pajvani, M Benito
Molecular and cellular biology 2017
Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis.
Marsh KM, Schipper D, Ferng AS, Johnson K, Fisher J, Knapp S, Dicken D, Khalpey Z
Lung 2017
The TSC Protein Complex Regulates Melanogenesis via AKT-GSK3β-β-Catenin-MITF
Juxiang Cao, Magdalena Tyburczy, Joel Moss, Thomas Darling, Hans R. Widlund, David J. Kwiatkowski
Journal of Clinical Investigation 2016
Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
S Llanos, JM García-Pedrero, L Morgado-Palacin, JP Rodrigo, M Serrano
Nature Communications 2016
Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling
KA Jewett, CA Christian, JT Bacos, KY Lee, J Zhu, NP Tsai
Molecular brain 2016
miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN
M Zhao, R Luo, Y Liu, L Gao, Z Fu, Q Fu, X Luo, Y Chen, X Deng, Z Liang, X Li, C Cheng, Z Liu, W Fang
Nature Communications 2016
The cilia-regulated proteasome and its role in the development of ciliopathies and cancer
C Gerhardt, T Leu, JM Lier, U Rüther
Cilia 2016
Abnormal serum microRNA profiles in tuberous sclerosis are normalized during treatment with everolimus: possible clinical implications
J Trelinska, W Fendler, I Dachowska, K Kotulska, S Jozwiak, K Antosik, P Gnys, M Borowiec, W Mlynarski
Orphanet Journal of Rare Diseases 2016
Intracellular signaling pathway regulation of myelination and remyelination in the CNS
JM Gaesser, SL Fyffe-Maricich
Experimental Neurology 2016
Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma
W Wei, YS Shin, M Xue, T Matsutani, K Masui, H Yang, S Ikegami, Y Gu, K Herrmann, D Johnson, X Ding, K Hwang, J Kim, J Zhou, Y Su, X Li, B Bonetti, R Chopra, CD James, WK Cavenee, TF Cloughesy, PS Mischel, JR Heath, B Gini
Cancer Cell 2016
Lysosomal recruitment of TSC2 is a universal response to cellular stress
C Demetriades, M Plescher, AA Teleman
Nature Communications 2016
mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria Mediated through the Down-Regulation of Autophagy
M Taneike, K Nishida, S Omiya, E Zarrinpashneh, T Misaka, R Kitazume-Taneike, R Austin, M Takaoka, O Yamaguchi, MJ Gambello, AM Shah, K Otsu, M Young
PloS one 2016
Functional kinomics establishes a critical node of volume-sensitive cation-Cl− cotransporter regulation in the mammalian brain
J Zhang, G Gao, G Begum, J Wang, AR Khanna, BE Shmukler, GM Daubner, P los Heros, P Davies, J Varghese, MI Bhuiyan, J Duan, J Zhang, D Duran, SL Alper, D Sun, SJ Elledge, DR Alessi, KT Kahle
Scientific Reports 2016
Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex
Y Guo, JR Dreier, J Cao, H Du, SR Granter, DJ Kwiatkowski, DJ Reiner
PloS one 2016
Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade
R Tyagi, N Shahani, L Gorgen, M Ferretti, W Pryor, PY Chen, S Swarnkar, PF Worley, K Karbstein, SH Snyder, S Subramaniam
Cell Reports 2015
Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways
J Zhang, S Ng, J Wang, J Zhou, SH Tan, N Yang, Q Lin, D Xia, HM Shen
Autophagy 2015
Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming
Y Wu, Y Li, H Zhang, Y Huang, P Zhao, Y Tang, X Qiu, Y Ying, W Li, S Ni, M Zhang, L Liu, Y Xu, Q Zhuang, Z Luo, C Benda, H Song, B Liu, L Lai, X Liu, HF Tse, X Bao, WY Chan, MA Esteban, B Qin, D Pei
Nature Cell Biology 2015
The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation
D Liu, Y Zhang, R Gharavi, HR Park, J Lee, S Siddiqui, R Telljohann, MR Nassar, RG Cutler, KG Becker, MP Mattson
Journal of Neurochemistry 2015
Interaction of polyamines and mTOR signaling in the synthesis of antizyme (AZ)
RM Ray, M Bavaria, LR Johnson
Cellular Signalling 2015
Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase
HY Ng, BG Oliver, JK Burgess, VP Krymskaya, JL Black, LM Moir
Journal of Cellular and Molecular Medicine 2015
TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1
M Plescher, AA Teleman, C Demetriades
Scientific Reports 2015
Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi
BE Housden, AJ Valvezan, C Kelley, R Sopko, Y Hu, C Roesel, S Lin, M Buckner, R Tao, B Yilmazel, SE Mohr, BD Manning, N Perrimon
Science signaling 2015
Class III PI3K regulates organismal glucose homeostasis by providing negative feedback on hepatic insulin signalling
I Nemazanyy, G Montagnac, RC Russell, L Morzyglod, AF Burnol, KL Guan, M Pende, G Panasyuk
Nature Communications 2015
PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex
MM Alves, GM Fuhler, KC Queiroz, J Scholma, S Goorden, J Anink, CA Spek, M Hoogeveen-Westerveld, MJ Bruno, M Nellist, Y Elgersma, E Aronica, MP Peppelenbosch
Scientific Reports 2015
Characterizing autism spectrum disorders by key biochemical pathways
M Subramanian, CK Timmerman, JL Schwartz, DL Pham, MK Meffert
Frontiers in neuroscience 2015
Growth factor signaling to mTORC1 by amino acid-laden macropinosomes
S Yoshida, R Pacitto, Y Yao, K Inoki, JA Swanson
The Journal of Cell Biology 2015
PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer
Y Zhang, X Wang, X Qin, X Wang, F Liu, E White, XF Zheng
EBioMedicine 2015
Transport to Rhebpress activity
A Garrido, M Brandt, N Djouder
Small GTPases 2015
Mediator Subunit Med28 Is Essential for Mouse Peri-Implantation Development and Pluripotency
L Li, RM Walsh, V Wagh, MF James, RL Beauchamp, YS Chang, JF Gusella, K Hochedlinger, V Ramesh, J Rajasingh
PloS one 2015
Golgi protein 73 activation of MMP-13 promotes hepatocellular carcinoma cell invasion.
Jin D, Tao J, Li D, Wang Y, Li L, Hu Z, Zhou Z, Chang X, Qu C, Zhang H
Oncotarget 2015
Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy
BJ Siroky, H Yin, BP Dixon, RJ Reichert, AR Hellmann, T Ramkumar, Z Tsuchihashi, M Bunni, J Dillon, PD Bell, JR Sampson, JJ Bissler
American journal of physiology. Renal physiology 2014
Small molecule adenosine 5′-monophosphate activated protein kinase (AMPK) modulators and human diseases
S Rana, EC Blowers, A Natarajan
Journal of Medicinal Chemistry 2014
Regulation of TORC1 in Response to Amino Acid Starvation via Lysosomal Recruitment of TSC2
C Demetriades, N Doumpas, AA Teleman
Cell 2014
Resveratrol prevents rapamycin-induced upregulation of autophagy and selectively induces apoptosis in TSC2-deficient cells
A Alayev, Y Sun, RB Snyder, SM Berger, JJ Yu, MK Holz
Cell cycle (Georgetown, Tex.) 2014
Signaling crosstalk between the mTOR complexes
J Xie, CG Proud
Translation 2014
Renal tumours in a Tsc2+/− mouse model do not show feedback inhibition of Akt and are effectively prevented by rapamycin
J Yang, M Kalogerou, PA Samsel, Y Zhang, DF Griffiths, J Gallacher, JR Sampson, MH Shen
Oncogene 2014
miR-126, a new modulator of innate immunity
C Ferretti, AL Cava
Cellular and Molecular Immunology 2014
The Regulation of Autophagy by Influenza A Virus
R Zhang, X Chi, S Wang, B Qi, X Yu, JL Chen
BioMed Research International 2014
Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner
R Miloslavski, E Cohen, A Avraham, Y Iluz, Z Hayouka, J Kasir, R Mudhasani, SN Jones, N Cybulski, MA Ruegg, O Larsson, V Gandin, A Rajakumar, I Topisirovic, O Meyuhas
Journal of Molecular Cell Biology 2014
Akt Phosphorylation and Regulation of Transketolase Is a Nodal Point for Amino Acid Control of Purine Synthesis
A Saha, S Connelly, J Jiang, S Zhuang, DT Amador, T Phan, RB Pilz, GR Boss
Molecular Cell 2014
REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to repress mTORC1 signaling
MD Dennis, CS Coleman, A Berg, LS Jefferson, SR Kimball
Science signaling 2014
Coordinated regulation of protein synthesis and degradation by mTORC1
Y Zhang, J Nicholatos, JR Dreier, SJ Ricoult, SB Widenmaier, GS Hotamisligil, DJ Kwiatkowski, BD Manning
Nature 2014
Beta interferon regulation of glucose metabolism is PI3K/Akt dependent and important for antiviral activity against coxsackievirus B3
JD Burke, LC Platanias, EN Fish
Journal of virology 2014
Ciliary transport regulates PDGF-AA/   signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity
NL Umberger, T Caspary
Molecular biology of the cell 2014
Rapamycin-Resistant Poly (ADP-Ribose) Polymerase-1 Overexpression Is a Potential Therapeutic Target in Lymphangioleiomyomatosis
Y Sun, D Gallacchi, EY Zhang, SB Reynolds, L Robinson, IA Malinowska, TT Chiou, AM Pereira, C Li, DJ Kwiatkowski, PS Lee, JJ Yu
American journal of respiratory cell and molecular biology 2014
Transcriptional repression of Sin3B by Bmi-1 prevents cellular senescence and is relieved by oncogene activation
T DiMauro, DJ Cantor, AJ Bainor, G David
Oncogene 2014
Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex
N Liang, C Zhang, P Dill, G Panasyuk, D Pion, V Koka, M Gallazzini, EN Olson, H Lam, EP Henske, Z Dong, U Apte, N Pallet, RL Johnson, F Terzi, DJ Kwiatkowski, JY Scoazec, G Martignoni, M Pende
Journal of Experimental Medicine 2014
A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy
B Ronan, O Flamand, L Vescovi, C Dureuil, L Durand, F Fassy, MF Bachelot, A Lamberton, M Mathieu, T Bertrand, JP Marquette, Y El-Ahmad, B Filoche-Romme, L Schio, C Garcia-Echeverria, H Goulaouic, B Pasquier
Nature Chemical Biology 2014
Combined regulation of mTORC1 and lysosomal acidification by GSK-3 suppresses autophagy and contributes to cancer cell growth
I Azoulay-Alfaguter, R Elya, L Avrahami, A Katz, H Eldar-Finkelman
Oncogene 2014
Rapamycin-Insensitive Up-Regulation of Adipocyte Phospholipase A2 in Tuberous Sclerosis and Lymphangioleiomyomatosis
C Li, E Zhang, Y Sun, PS Lee, Y Zhan, Y Guo, JC Osorio, IO Rosas, KF Xu, DJ Kwiatkowski, JJ Yu, DJ Reiner
PloS one 2014
Reassessment of the Role of TSC, mTORC1 and MicroRNAs in Amino Acids-Meditated Translational Control of TOP mRNAs
I Patursky-Polischuk, J Kasir, R Miloslavski, Z Hayouka, M Hausner-Hanochi, M Stolovich-Rain, P Tsukerman, M Biton, R Mudhasani, SN Jones, O Meyuhas, T Preiss
PloS one 2014
Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin
ND Yang, SH Tan, S Ng, Y Shi, J Zhou, KS Tan, WS Wong, HM Shen
The Journal of biological chemistry 2014
rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9
KW Mok, DD Mruk, CY Cheng
Journal of cell science 2014
PDK4 Protein Promotes Tumorigenesis through Activation of cAMP-response Element-binding Protein (CREB)-Ras Homolog Enriched in Brain (RHEB)-mTORC1 Signaling Cascade
Z Liu, X Chen, Y Wang, H Peng, Y Wang, Y Jing, H Zhang
The Journal of biological chemistry 2014
AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
V Cianfanelli, C Fuoco, M Lorente, M Salazar, F Quondamatteo, PF Gherardini, DD Zio, F Nazio, M Antonioli, M DOrazio, T Skobo, M Bordi, M Rohde, LD Valle, M Helmer-Citterich, C Gretzmeier, J Dengjel, GM Fimia, M Piacentini, SD Bartolomeo, G Velasco, F Cecconi
Nature Cell Biology 2014
PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells
A Yeomans, E Lemm, S Wilmore, BE Cavell, B Valle-Argos, S Krysov, MS Hidalgo, E Leonard, AE Willis, F Forconi, FK Stevenson, AJ Steele, MJ Coldwell, G Packham
Oncotarget 2014
Balanced mTORC1 Activity in Oligodendrocytes Is Required for Accurate CNS Myelination
F Lebrun-Julien, L Bachmann, C Norrmen, M Trotzmuller, H Kofeler, MA Ruegg, MN Hall, U Suter
The Journal of neuroscience : the official journal of the Society for Neuroscience 2014
A novel androgen-regulated isoform of the TSC2 tumour suppressor gene increases cell proliferation.
Munkley J, Rajan P, Lafferty NP, Dalgliesh C, Jackson RM, Robson CN, Leung HY, Elliott DJ
Oncotarget 2014
Subependymal giant cell astrocytoma: current concepts, management, and future directions.
Ouyang T, Zhang N, Benjamin T, Wang L, Jiao J, Zhao Y, Chen J
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2014
Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis
L Jiang, L Xu, J Mao, J Li, L Fang, Y Zhou, W Liu, W He, AZ Zhao, J Yang, C Dai
Journal of the American Society of Nephrology : JASN 2013
FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade
S Kuchay, S Duan, E Schenkein, A Peschiaroli, A Saraf, L Florens, MP Washburn, M Pagano
Nature Cell Biology 2013
Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion
J Zhou, SH Tan, V Nicolas, C Bauvy, ND Yang, J Zhang, Y Xue, P Codogno, HM Shen
Cell Research 2013
mTOR signaling for biological control and cancer
A Alayev, MK Holz
Journal of Cellular Physiology 2013
The Effect of Gartanin, a Naturally Occurring Xanthone in Mangosteen Juice, on the mTOR Pathway, Autophagy, Apoptosis, and the Growth of Human Urinary Bladder Cancer Cell Lines
Z Liu, M Antalek, L Nguyen, X Li, X Tian, A Le, X Zi
Nutrition and Cancer 2013
Nutrients and growth factors in mTORC1 activation
A Efeyan, DM Sabatini
Biochemical Society Transactions 2013
Bile acid-induced inflammatory signaling in mice lacking Foxa2 in the liver leads to activation of mTOR and age-onset obesity
IM Bochkis, S Shin, KH Kaestner
Molecular Metabolism 2013
Autophagy negatively regulates early axon growth in cortical neurons
BK Ban, MH Jun, HH Ryu, DJ Jang, ST Ahmad, JA Lee
Molecular and cellular biology 2013
mTORC1 inhibition is required for sensitivity to PI3K p110α inhibitors in PIK3CA-mutant breast cancer
M Elkabets, S Vora, D Juric, N Morse, M Mino-Kenudson, T Muranen, J Tao, AB Campos, J Rodon, YH Ibrahim, V Serra, V Rodrik-Outmezguine, S Hazra, S Singh, P Kim, C Quadt, M Liu, A Huang, N Rosen, JA Engelman, M Scaltriti, J Baselga
Science Translational Medicine 2013
Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress
RM Young, D Ackerman, ZL Quinn, A Mancuso, M Gruber, L Liu, DN Giannoukos, E Bobrovnikova-Marjon, JA Diehl, B Keith, MC Simon
Genes & development 2013
Targeting the PI3K-AKT-mTOR signaling network in cancer
KH Khan, TA Yap, L Yan, D Cunningham
Chinese journal of cancer 2013
p38α senses environmental stress to control innate immune responses via mechanistic target of rapamycin
K Katholnig, CC Kaltenecker, H Hayakawa, M Rosner, C Lassnig, GJ Zlabinger, M Gaestel, M Müller, M Hengstschläger, WH Hörl, JM Park, MD Säemann, T Weichhart
Journal of immunology (Baltimore, Md. : 1950) 2013
Mammalian target of rapamycin complex 1 (mTORC1) enhances bortezomib-induced death in tuberous sclerosis complex (TSC)-null cells by a c-MYC-dependent induction of the unfolded protein response
JT Babcock, HB Nguyen, Y He, JW Hendricks, RC Wek, LA Quilliam
The Journal of biological chemistry 2013
mTORC1 Dependent Regulation of REDD1 Protein Stability
CY Tan, T Hagen, TG Hofmann
PloS one 2013
MC1R Is a Potent Regulator of PTEN after UV Exposure in Melanocytes
J Cao, L Wan, E Hacker, X Dai, S Lenna, C Jimenez-Cervantes, Y Wang, NR Leslie, GX Xu, HR Widlund, B Ryu, RM Alani, K Dutton-Regester, CR Goding, NK Hayward, W Wei, R Cui
Molecular Cell 2013
MicroRNA-21 is Induced by Rapamycin in a Model of Tuberous Sclerosis (TSC) and Lymphangioleiomyomatosis (LAM)
AJ Trindade, DA Medvetz, NA Neuman, F Myachina, J Yu, C Priolo, EP Henske, A Navarro
PloS one 2013
Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish
SH Kim, ML Kowalski, RP Carson, LR Bridges, KC Ess
Disease models & mechanisms 2013
mTORC1 and p53: clash of the gods?
Hasty P, Sharp ZD, Curiel TJ, Campisi J
Cell cycle (Georgetown, Tex.) 2013
The Cdk inhibitor flavopiridol enhances temozolomide-induced cytotoxicity in human glioma cells.
Hayashi T, Adachi K, Ohba S, Hirose Y
Journal of Neuro-Oncology 2013
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
Couty S, Westwood IM, Kalusa A, Cano C, Travers J, Boxall K, Chow CL, Burns S, Schmitt J, Pickard L, Barillari C, McAndrew PC, Clarke PA, Linardopoulos S, Griffin RJ, Aherne GW, Raynaud FI, Workman P, Jones K, van Montfort RL
Oncotarget 2013
Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress
S Deegan, S Saveljeva, AM Gorman, A Samali
Cellular and Molecular Life Sciences 2012
The functions and regulation of the PTEN tumour suppressor
MS Song, L Salmena, PP Pandolfi
Nature Reviews Molecular Cell Biology 2012
Selenite targets eIF4E-binding protein-1 to inhibit translation initiation and induce the assembly of non-canonical stress granules
K Fujimura, AT Sasaki, P Anderson
Nucleic Acids Research 2012
Activation of PI3K/AKT and MAPK Pathway through a PDGFRβ-Dependent Feedback Loop Is Involved in Rapamycin Resistance in Hepatocellular Carcinoma
QL Li, FM Gu, Z Wang, JH Jiang, LQ Yao, CJ Tan, XY Huang, AW Ke, Z Dai, J Fan, J Zhou
PloS one 2012
Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance
SK Bose, S Shrivastava, K Meyer, RB Ray, R Ray
Journal of virology 2012
mTORC1 signaling and regulation of pancreatic β-cell mass
M Blandino-Rosano, AY Chen, JO Scheys, EU Alejandro, AP Gould, T Taranukha, L Elghazi, C Cras-Méneur, E Bernal-Mizrachi
Cell cycle (Georgetown, Tex.) 2012
Mitochondria and organismal longevity
AB Hwang, DE Jeong, SJ Lee
Current genomics 2012
Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival
A Efeyan, R Zoncu, S Chang, I Gumper, H Snitkin, RL Wolfson, O Kirak, DD Sabatini, DM Sabatini
Nature 2012
mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development
H Peng, J Liu, Q Sun, R Chen, Y Wang, J Duan, C Li, B Li, Y Jing, X Chen, Q Mao, KF Xu, CL Walker, J Li, J Wang, H Zhang
Oncogene 2012
TSC2 modulates cell adhesion and migration via integrin-α1β1
LM Moir, JL Black, VP Krymskaya
American journal of physiology. Lung cellular and molecular physiology 2012
Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict head and neck cancer patient second primary tumor/recurrence risk and response to retinoid chemoprevention
MA Hildebrandt, SM Lippman, CJ Etzel, E Kim, JJ Lee, FR Khuri, MR Spitz, R Lotan, WK Hong, X Wu
Clinical cancer research 2012
Rab5 proteins regulate activation and localization of target of rapamycin complex 1
D Bridges, K Fisher, SN Zolov, T Xiong, K Inoki, LS Weisman, AR Saltiel
The Journal of biological chemistry 2012
Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling
BD Fonseca, GH Diering, MA Bidinosti, K Dalal, T Alain, AD Balgi, R Forestieri, M Nodwell, CV Rajadurai, C Gunaratnam, AR Tee, F Duong, RJ Andersen, J Orlowski, M Numata, N Sonenberg, M Roberge
The Journal of biological chemistry 2012
Deconvoluting mTOR biology
JD Weber, DH Gutmann
Cell cycle (Georgetown, Tex.) 2012
mTOR Regulates Cellular Iron Homeostasis through Tristetraprolin
M Bayeva, A Khechaduri, S Puig, HC Chang, S Patial, PJ Blackshear, H Ardehali
Cell Metabolism 2012
TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1
CC Dibble, W Elis, S Menon, W Qin, J Klekota, JM Asara, PM Finan, DJ Kwiatkowski, LO Murphy, BD Manning
Molecular Cell 2012
Nitazoxanide Stimulates Autophagy and Inhibits mTORC1 Signaling and Intracellular Proliferation of Mycobacterium tuberculosis
KK Lam, X Zheng, R Forestieri, AD Balgi, M Nodwell, S Vollett, HJ Anderson, RJ Andersen, Y Av-Gay, M Roberge, V Deretic
PLoS pathogens 2012
TSC1/2 Signaling Complex Is Essential for Peripheral Naïve CD8+ T Cell Survival and Homeostasis in Mice
L Zhang, H Zhang, L Li, Y Xiao, E Rao, Z Miao, H Chen, L Sun, H Li, G Liu, Y Zhao, B Ryffel
PloS one 2012
Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion
DA Medvetz, D Khabibullin, V Hariharan, PP Ongusaha, EA Goncharova, T Schlechter, TN Darling, I Hofmann, VP Krymskaya, JK Liao, H Huang, EP Henske, SC Nam
PloS one 2012
The TSC1-TSC2 complex consists of multiple TSC1 and TSC2 subunits
M Hoogeveen-Westerveld, L van Unen, A van den Ouweland, D Halley, A Hoogeveen, M Nellist
BMC Biochemistry 2012
Aberrant CD8+ T-Cell Responses and Memory Differentiation upon Viral Infection of an Ataxia-Telangiectasia Mouse Model Driven by Hyper-Activated Akt and mTORC1 Signaling
AD D'Souza, IA Parish, SE McKay, SM Kaech, GS Shadel
The American Journal of Pathology 2011
Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives
M Dufour, A Dormond-Meuwly, N Demartines, O Dormond
Cancers 2011
The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic β-cell mass: implications in the development of type-2 diabetes
J Xie, TP Herbert
Cellular and Molecular Life Sciences 2011
Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin
AJ Malhowski, H Hira, S Bashiruddin, R Warburton, J Goto, B Robert, DJ Kwiatkowski, GA Finlay
Human Molecular Genetics 2011
Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth
Q Sun, X Chen, J Ma, H Peng, F Wang, X Zha, Y Wang, Y Jing, H Yang, R Chen, L Chang, Y Zhang, J Goto, H Onda, T Chen, MR Wang, Y Lu, H You, D Kwiatkowski, H Zhang
Proceedings of the National Academy of Sciences 2011
mTORC2 Is Required for Proliferation and Survival of TSC2-Null Cells ▿
EA Goncharova, DA Goncharov, H Li, W Pimtong, S Lu, I Khavin, VP Krymskaya
Molecular and cellular biology 2011
cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity
J Xie, GA Ponuwei, CE Moore, GB Willars, AR Tee, TP Herbert
Cellular Signalling 2011
Phosphorylation of Raptor by p38β Participates in Arsenite-induced Mammalian Target of Rapamycin Complex 1 (mTORC1) Activation*
XN Wu, XK Wang, SQ Wu, J Lu, M Zheng, YH Wang, H Zhou, H Zhang, J Han
The Journal of biological chemistry 2011
Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner
S Banerjee, NR Crouse, RJ Emnett, SM Gianino, DH Gutmann
Proceedings of the National Academy of Sciences 2011
Unrestrained mammalian target of rapamycin complexes 1 and 2 increase expression of phosphatase and tensin homolog deleted on chromosome 10 to regulate phosphorylation of Akt kinase
F Das, N Ghosh-Choudhury, N Dey, CC Mandal, L Mahimainathan, BS Kasinath, HE Abboud, GG Choudhury
The Journal of biological chemistry 2011
Complex Inhibitory Effects of Nitric Oxide on Autophagy
S Sarkar, VI Korolchuk, M Renna, S Imarisio, A Fleming, A Williams, M Garcia-Arencibia, C Rose, S Luo, BR Underwood, G Kroemer, CJ O'Kane, DC Rubinsztein
Molecular Cell 2011
Regulation of TFEB and V-ATPases by mTORC1: Regulation of TFEB and V-ATPases by mTORC1
S Peña-Llopis, S Vega-Rubin-de-Celis, JC Schwartz, NC Wolff, TA Tran, L Zou, XJ Xie, DR Corey, J Brugarolas
The EMBO Journal 2011
The Glycolytic Shift in Fumarate-Hydratase-Deficient Kidney Cancer Lowers AMPK Levels, Increases Anabolic Propensities and Lowers Cellular Iron Levels
WH Tong, C Sourbier, G Kovtunovych, SY Jeong, M Vira, M Ghosh, VV Romero, R Sougrat, S Vaulont, B Viollet, YS Kim, S Lee, J Trepel, R Srinivasan, G Bratslavsky, Y Yang, WM Linehan, TA Rouault
Cancer Cell 2011
Interplay between FOXO, TOR, and Akt
N Hay
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2011
Regulation of mTORC1 Signaling by pH
AD Balgi, GH Diering, E Donohue, KK Lam, BD Fonseca, C Zimmerman, M Numata, M Roberge, M Polymenis
PloS one 2011
Hypergrowth mTORC1 Signals Translationally Activate the ARF Tumor Suppressor Checkpoint
AP Miceli, AJ Saporita, JD Weber
Molecular and cellular biology 2011
Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks
S Alers, AS Loffler, S Wesselborg, B Stork
Molecular and cellular biology 2011
Progeria, rapamycin and normal aging: recent breakthrough.
Blagosklonny MV
Aging 2011
Rapamycin-Insensitive Up-Regulation of MMP2 and Other Genes in Tuberous Sclerosis Complex 2–Deficient Lymphangioleiomyomatosis-Like Cells
PS Lee, SW Tsang, MA Moses, Z Trayes-Gibson, LL Hsiao, R Jensen, R Squillace, DJ Kwiatkowski
American journal of respiratory cell and molecular biology 2010
Phosphoinositide 3-kinase in Health and Disease
C Rommel, B Vanhaesebroeck, PK Vogt
2010
ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
A Alexander, SL Cai, J Kim, A Nanez, M Sahin, KH MacLean, K Inoki, KL Guan, J Shen, MD Person, D Kusewitt, GB Mills, MB Kastan, CL Walker
Proceedings of the National Academy of Sciences 2010
Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress
S Sengupta, TR Peterson, DM Sabatini
Molecular Cell 2010
Lymphangioleiomyomatosis and TSC2-/- cells
TN Darling, G Pacheco-Rodriguez, A Gorio, E Lesma, C Walker, J Moss
Lymphatic Research and Biology 2010
Laforin, the most common protein mutated in Lafora disease, regulates autophagy
C Aguado, S Sarkar, VI Korolchuk, O Criado, S Vernia, P Boya, P Sanz, SR de Córdoba, E Knecht, DC Rubinsztein
Human Molecular Genetics 2010
SIRT1 negatively regulates the mammalian target of rapamycin
HS Ghosh, M McBurney, PD Robbins
PloS one 2010
Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage
P Chakrabarti, T English, J Shi, CM Smas, KV Kandror
Diabetes 2010
Tuberous Sclerosis Complex 1: An Epithelial Tumor Suppressor Essential to Prevent Spontaneous Prostate Cancer in Aged Mice
RD Kladney, RD Cardiff, DJ Kwiatkowski, GG Chiang, JD Weber, JM Arbeit, ZH Lu
Cancer research 2010
Resveratrol Inhibits mTOR Signaling by Promoting the Interaction between mTOR and DEPTOR*
M Liu, SA Wilk, A Wang, L Zhou, RH Wang, W Ogawa, C Deng, LQ Dong, F Liu
The Journal of biological chemistry 2010
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
K Düvel, JL Yecies, S Menon, P Raman, AI Lipovsky, AL Souza, E Triantafellow, Q Ma, R Gorski, S Cleaver, MG Heiden, JP MacKeigan, PM Finan, CB Clish, LO Murphy, BD Manning
Molecular Cell 2010
FoxOs Inhibit mTORC1 and Activate Akt by Inducing the Expression of Sestrin3 and Rictor
CC Chen, SM Jeon, PT Bhaskar, V Nogueira, D Sundararajan, I Tonic, Y Park, N Hay
Developmental Cell 2010
14-3-3γ Induces Oncogenic Transformation by Stimulating MAP Kinase and PI3K Signaling
VM Radhakrishnan, JD Martinez, MV Blagosklonny
PloS one 2010
mTORC1-S6K Activation by Endotoxin Contributes to Cytokine Up-Regulation and Early Lethality in Animals
PS Lee, AS Wilhelmson, AP Hubner, SB Reynolds, DA Gallacchi, TT Chiou, DJ Kwiatkowski, J Deng
PloS one 2010
Carboxy Terminal Tail of Polycystin-1 Regulates Localization of TSC2 to Repress mTOR
R Dere, PD Wilson, RN Sandford, CL Walker, MV Blagosklonny
PloS one 2010
mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling
LA Julien, A Carriere, J Moreau, PP Roux
Molecular and cellular biology 2010
The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway.
Korotchkina LG, Leontieva OV, Bukreeva EI, Demidenko ZN, Gudkov AV, Blagosklonny MV
Aging 2010
Mammalian Target of Rapamycin Regulates Cell Differentiation through STAT3-p63-Jagged-Notch Cascade
Jianhui Ma, Yan Meng, David J. Kwiatkowski, Xinxin Chen, Haiyong Peng, Qian Sun, Xiaojun Zha, Fang Wang, Ying Wang, Yanling Jing, Shu Zhang, Rongrong Chen, Lianmei Wang, Erxi Wu, Guifang Cai, Izabela Malinowska-Kolodziej, Qi Liao, Yuqin Liu, Yi Zhao, Qiang Sun, Kaifeng Xu, Jianwu Dai, Jiahuai Han, Lizi Wu, Robert Chunhua Zhao, Huangxuan Shen, Hongbing Zhang
Journal of Clinical Investigation 2009
NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth
MF James, S Han, C Polizzano, SR Plotkin, BD Manning, AO Stemmer-Rachamimov, JF Gusella, V Ramesh
Molecular and cellular biology 2009
Regulation of CLU gene expression by oncogenes and epigenetic factors: Implications for tumorigenesis
A Sala, S Bettuzzi, S Pucci, O Chayka, M Dews, A Thomas-Tikhonenko
Advances in cancer research 2009
Emerging evidence of a link between the polycystins and the mTOR pathways
A Boletta
PathoGenetics 2009
Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway
HH Zhang, J Huang, K Düvel, B Boback, S Wu, RM Squillace, CL Wu, BD Manning
PloS one 2009
The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis
W Wang, A Fridman, W Blackledge, S Connelly, IA Wilson, RB Pilz, GR Boss
The Journal of biological chemistry 2009
TSC2 deficiency increases PTEN via HIF1alpha
L Mahimainathan, N Ghosh-Choudhury, B Venkatesan, F Das, CC Mandal, N Dey, SL Habib, BS Kasinath, HE Abboud, GG Choudhury
The Journal of biological chemistry 2009
From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis
D Ehninger, PJ de Vries, AJ Silva
Journal of intellectual disability research : JIDR 2009
Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors
J Huang, S Wu, CL Wu, BD Manning
Cancer research 2009
Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis
K Pollizzi, I Malinowska-Kolodziej, M Stumm, H Lane, D Kwiatkowski
Molecular Cancer 2009
A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles
K Pollizzi, I Malinowska-Kolodziej, C Doughty, C Betz, J Ma, J Goto, DJ Kwiatkowski
Human Molecular Genetics 2009
TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity
MC Liang, J Ma, L Chen, P Kozlowski, W Qin, D Li, J Goto, T Shimamura, DN Hayes, M Meyerson, DJ Kwiatkowski, KK Wong
Oncogene 2009
mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome
DB Shackelford, DS Vasquez, J Corbeil, S Wu, M Leblanc, CL Wu, DR Vera, RJ Shaw
Proceedings of the National Academy of Sciences 2009
Lean and obese Zucker rats exhibit different patterns of p70s6 kinase regulation in the tibialis anterior muscle in response to high-force muscle contraction
A Katta, SK Karkala, M Wu, S Meduru, DH Desai, KM Rice, ER Blough
Muscle & Nerve 2009
Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition
M Breuleux, M Klopfenstein, C Stephan, CA Doughty, L Barys, SM Maira, D Kwiatkowski, HA Lane
Molecular cancer therapeutics 2009
Akt-dependent and -independent mechanisms of mTOR regulation in cancer
RM Memmott, PA Dennis
Cellular Signalling 2009
Pancreatic Endocrine Tumors: Expression Profiling Evidences a Role for AKT-mTOR Pathway
E Missiaglia, I Dalai, S Barbi, S Beghelli, M Falconi, M Peruta, L Piemonti, G Capurso, AD Florio, G Fave, P Pederzoli, CM Croce, A Scarpa
Journal of Clinical Oncology 2009
Screen for Chemical Modulators of Autophagy Reveals Novel Therapeutic Inhibitors of mTORC1 Signaling
AD Balgi, BD Fonseca, E Donohue, TC Tsang, P Lajoie, CG Proud, IR Nabi, M Roberge, Y Cao
PloS one 2009
The TSC-mTOR Pathway Mediates Translational Activation of TOP mRNAs by Insulin Largely in a Raptor- or Rictor-Independent Manner
I Patursky-Polischuk, M Stolovich-Rain, M Hausner-Hanochi, J Kasir, N Cybulski, J Avruch, MA Rüegg, MN Hall, O Meyuhas
Molecular and cellular biology 2009
A novel feedback loop leads to activation of MAPK pathway by mTORC1 inhibitors
Arkaitz Carracedo, Li Ma, Julie Teruya-Feldstein, Federico Rojo, Leonardo Salmena, Andrea Alimonti, Ainara Egia, Atsuo T. Sasaki, George Thomas, Sara C. Kozma, Antonella Papa, Caterina Nardella, Lewis C. Cantley, Jose Baselga and Pier Paolo Pandolfi
Journal of Clinical Investigation 2008
mTORC1 promotes survival through translational control of Mcl-1
JR Mills, Y Hippo, F Robert, SM Chen, A Malina, CJ Lin, U Trojahn, HG Wendel, A Charest, RT Bronson, SC Kogan, R Nadon, DE Housman, SW Lowe, J Pelletier
Proceedings of the National Academy of Sciences 2008
AMP-Activated Protein Kinase Signaling Results in Cytoplasmic Sequestration of p27
JD Short, KD Houston, R Dere, SL Cai, J Kim, CL Johnson, RR Broaddus, J Shen, S Miyamoto, F Tamanoi, D Kwiatkowski, GB Mills, CL Walker
Cancer research 2008
PHLiPPing the switch on Akt and protein kinase C signaling
J Brognard, AC Newton
Trends in endocrinology and metabolism: TEM 2008
The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway
TR Hartman, D Liu, JT Zilfou, V Robb, T Morrison, T Watnick, EP Henske
Human Molecular Genetics 2008
Rapamycin and mTOR kinase inhibitors
LM Ballou, RZ Lin
Journal of Chemical Biology 2008
Anti-EGFR antibody efficiently and specifically inhibits human TSC2-/- smooth muscle cell proliferation. Possible treatment options for TSC and LAM
E Lesma, V Grande, S Ancona, S Carelli, AM di Giulio, A Gorio
PloS one 2008
Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction
Z Lin, JV Sugai, Q Jin, LA Chandler, WV Giannobile
Journal of Periodontal Research 2008
Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function
L Meikle, K Pollizzi, A Egnor, I Kramvis, H Lane, M Sahin, DJ Kwiatkowski
The Journal of neuroscience : the official journal of the Society for Neuroscience 2008
FOXO-regulated transcription restricts overgrowth of Tsc mutant organs
KF Harvey, J Mattila, A Sofer, FC Bennett, MR Ramsey, LW Ellisen, O Puig, IK Hariharan
The Journal of Cell Biology 2008
Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling
MP DeYoung, P Horak, A Sofer, D Sgroi, LW Ellisen
Genes & development 2008
Smooth muscle-like cells in pulmonary lymphangioleiomyomatosis
VP Krymskaya
Proceedings of the American Thoracic Society 2008
Platelet-Derived Growth Factor-D Overexpression Contributes to Epithelial-Mesenchymal Transition of PC3 Prostate Cancer Cells
D Kong, Z Wang, SH Sarkar, Y Li, S Banerjee, A Saliganan, HR Kim, ML Cher, FH Sarkar
Stem Cells 2008
A reliable cell-based assay for testing unclassified TSC2 gene variants
R Coevoets, S Arican, M Hoogeveen-Westerveld, E Simons, A Ouweland, D Halley, M Nellist
European Journal of Human Genetics 2008
Missense mutations to the TSC1 gene cause tuberous sclerosis complex
M Nellist, D Heuvel, D Schluep, C Exalto, M Goedbloed, A Maat-Kievit, T Essen, K Spaendonck-Zwarts, F Jansen, P Helderman, G Bartalini, O Vierimaa, M Penttinen, J Ende, A Ouweland, D Halley
European Journal of Human Genetics 2008
cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner
EM Smith, CG Proud
The EMBO Journal 2008
Functional characterisation of the TSC1–TSC2 complex to assess multiple TSC2 variants identified in single families affected by tuberous sclerosis complex
M Nellist, Ő Sancak, M Goedbloed, A Adriaans, M Wessels, A Maat-Kievit, M Baars, C Dommering, A Ouweland, D Halley
BMC Medical Genetics 2008
Comprehensive Dissection of PDGF-PDGFR Signaling Pathways in PDGFR Genetically Defined Cells
E Wu, N Palmer, Z Tian, AP Moseman, M Galdzicki, X Wang, B Berger, H Zhang, IS Kohane, S Rutherford
PloS one 2008
Mammalian Target of Rapamycin Repression by 3,3′-Diindolylmethane Inhibits Invasion and Angiogenesis in Platelet-Derived Growth Factor-D–Overexpressing PC3 Cells
D Kong, S Banerjee, W Huang, Y Li, Z Wang, HR Kim, FH Sarkar
Cancer research 2008
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
J Huang, BD Manning
Biochemical Journal 2008
The TSC1-TSC2 Complex Is Required for Proper Activation of mTOR Complex 2
J Huang, CC Dibble, M Matsuzaki, BD Manning
Molecular and cellular biology 2008
Deconstructing feedback-signaling networks to improve anticancer therapy with mTORC1 inhibitors.
Carracedo A, Baselga J, Pandolfi PP
Cell cycle (Georgetown, Tex.) 2008
PDGF receptors are critical for PI3K/AKT activation and negatively regulated by mTOR
Hongbing Zhang, Natalia Bajraszewski, Erxi Wu, Hongwei Wang, Annie P. Mose, Sandra L. Dabora, James D. Griffin, David J. Kwiatkowski
Journal of Clinical Investigation 2007
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2
Olivier Le Bacquer, Emmanuel Petroulakis, Sabina Paglialunga, Francis Poulin, Denis Richard, Katherine Cianflone, Nahum Sonenberg
Journal of Clinical Investigation 2007
Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53
CH Lee, K Inoki, M Karbowniczek, E Petroulakis, N Sonenberg, EP Henske, KL Guan
The EMBO Journal 2007
Effects of rapamycin on gene expression, morphology, and electrophysiological properties of rat hippocampal neurons
S Rüegg, M Baybis, H Juul, M Dichter, PB Crino
Epilepsy Research 2007
Molecular Pathogenesis of Lymphangioleiomyomatosis: Lessons Learned from Orphans
SC Juvet, FX McCormack, DJ Kwiatkowski, GP Downey
American journal of respiratory cell and molecular biology 2007
Tuberous Sclerosis Complex Proteins 1 and 2 Control Serum-Dependent Translation in a TOP-Dependent and -Independent Manner
B Bilanges, R Argonza-Barrett, M Kolesnichenko, C Skinner, M Nair, M Chen, D Stokoe
Molecular and cellular biology 2007
c-myc Repression of TSC2 Contributes to Control of Translation Initiation and Myc-Induced Transformation
MJ Ravitz, L Chen, M Lynch, EV Schmidt
Cancer research 2007
S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt
HH Zhang, AI Lipovsky, CC Dibble, M Sahin, BD Manning
Molecular Cell 2006
Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis
OJ Shah, T Hunter
Molecular and cellular biology 2006
Systems analysis of circadian time-dependent neuronal epidermal growth factor receptor signaling
DE Zak, H Hao, R Vadigepalli, GM Miller, BA Ogunnaike, JS Schwaber
Genome biology 2006
Rac1-null mouse embryonic fibroblasts are motile and respond to platelet-derived growth factor
L Vidali, F Chen, G Cicchetti, Y Ohta, DJ Kwiatkowski
Molecular biology of the cell 2006
Abnormal Growth of Smooth Muscle–Like Cells in Lymphangioleiomyomatosis: Role for Tumor Suppressor TSC2
EA Goncharova, DA Goncharov, M Spaits, DJ Noonan, E Talovskaya, A Eszterhas, VP Krymskaya
American journal of respiratory cell and molecular biology 2006
The coordinate regulation of the p53 and mTOR pathways in cells
Z Feng, H Zhang, AJ Levine, S Jin
Proceedings of the National Academy of Sciences 2005
Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
BD Manning, MN Logsdon, AI Lipovsky, D Abbott, DJ Kwiatkowski, LC Cantley
Genes & development 2005
Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression
L Ma, J Teruya-Feldstein, N Behrendt, Z Chen, T Noda, O Hino, C Cordon-Cardo, PP Pandolfi
Genes & development 2005
Regulation of mTOR and cell growth in response to energy stress by REDD1
A Sofer, K Lei, CM Johannessen, LW Ellisen
Molecular and cellular biology 2005
The NF1 tumor suppressor critically regulates TSC2 and mTOR
CM Johannessen, EE Reczek, MF James, H Brems, E Legius, K Cichowski
Proceedings of the National Academy of Sciences 2005
Identification of FIP200 interaction with the TSC1–TSC2 complex and its role in regulation of cell size control
B Gan, ZK Melkoumian, X Wu, KL Guan, JL Guan
The Journal of Cell Biology 2005
Balancing Akt with S6K: Figure 1.: implications for both metabolic diseases and tumorigenesis
BD Manning
The Journal of Cell Biology 2004
TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase
E Goncharova, D Goncharov, D Noonan, VP Krymskaya
The Journal of Cell Biology 2004
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
J Brugarolas, K Lei, RL Hurley, BD Manning, JH Reiling, E Hafen, LA Witters, LW Ellisen, WG Kaelin
Genes & development 2004
Amino acids as regulators of gene expression
SR Kimball, LS Jefferson
Nutrition & Metabolism 2004
A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin
GJ Browne, CG Proud
Molecular and cellular biology 2004
The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins
LS Harrington, GM Findlay, A Gray, T Tolkacheva, S Wigfield, H Rebholz, J Barnett, NR Leslie, S Cheng, PR Shepherd, I Gout, CP Downes, RF Lamb
The Journal of Cell Biology 2004

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