The TSC1–TSC2 complex: a molecular switchboard controlling cell growth

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works

AKT/PKB signaling: navigating downstream

Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115 · see citing works

TOR signaling in growth and metabolism

Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works

Upstream and downstream of mTOR

Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · see citing works

TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival

Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works

TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works

Defining the role of mTOR in cancer

Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833 · see citing works

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

Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works

Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB

Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,659 · see citing works

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

Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097 · see citing works

Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast

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

Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911 · see citing works

Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control

Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886 · see citing works

The Tuberous Sclerosis Complex

Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793 · see citing works

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

Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677 · see citing works

Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34

Slegtenhorst, M. V., Hoogt, R. D., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Ouweland, A. V. D., Halley, D., Young, J., et al. (1997) · Science · doi:10.1126/science.277.5327.805 · Cited by 1,648 · see citing works

Identification and characterization of the tuberous sclerosis gene on chromosome 16

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Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway

Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00568-3 · Cited by 1,555 · see citing works

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

Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes &amp; Development · doi:10.1101/gad.1256804 · Cited by 1,384 · see citing works

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

Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.055 · Cited by 1,377 · see citing works

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

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Phosphorylation and Functional Inactivation of TSC2 by Erk

Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268 · see citing works

Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression

Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,250 · see citing works

Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

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PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase

Sancak, Y., Thoreen, C. C., Peterson, T. R., Lindquist, R. A., Kang, S. A., Spooner, E., Carr, S. A., & Sabatini, D. M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.003 · Cited by 1,236 · see citing works

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

Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · see citing works

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

Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., & Sabatini, D. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1432 · Cited by 1,139 · see citing works

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

Harrington, L. S., Findlay, G. M., Gray, A., Толкачева, Т. А., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403069 · Cited by 1,123 · see citing works

Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E

Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes &amp; Development · doi:10.1101/gad.995802 · Cited by 1,093 · see citing works

The LKB1 tumor suppressor negatively regulates mTOR signaling

Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,067 · see citing works

Insulin Activation of Rheb, a Mediator of mTOR/S6K/4E-BP Signaling, Is Inhibited by TSC1 and 2

Garami, A., Zwartkruis, F. J. T., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., & Thomas, G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00220-x · Cited by 1,043 · see citing works

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

Neshat, M., Mellinghoff, I., Tran, C., Stiles, B. L., Thomas, G., Petersen, R., Frost, P., Gibbons, J., Wu, H., & Sawyers, C. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.171076798 · Cited by 1,033 · see citing works

Rheb Binds and Regulates the mTOR Kinase

Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., & Avruch, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.053 · Cited by 1,005 · see citing works

mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways

Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964 · see citing works

Mammalian TOR: a homeostatic ATP sensor

Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001) · Science · doi:10.1126/science.1063518 · Cited by 962 · see citing works

Akt regulates growth by directly phosphorylating Tsc2

Potter, C. J., Pedraza, L. G., & Xu, T. (2002) · Nature Cell Biology · doi:10.1038/ncb840 · Cited by 959 · see citing works

Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins

Zhang, Y., Gao, X., Saucedo, L. J., Ru, B., Edgar, B. A., & Pan, D. (2003) · Nature Cell Biology · doi:10.1038/ncb999 · Cited by 924 · see citing works

Hierarchical phosphorylation of the translation inhibitor 4E-BP1

Gingras, A.-C., Raught, B., Gygi, S. P., Niedzwiecka, A., Miron, M., Burley, S. K., Polakiewicz, R. D., Wyslouch-Cieszynska, A., Aebersold, R., & Sonenberg, N. (2001) · Genes &amp; Development · doi:10.1101/gad.912401 · Cited by 883 · see citing works

Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling

Tee, A. R., Fingar, D. C., Manning, B. D., Kwiatkowski, D. J., Cantley, L. C., & Blenis, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202476899 · Cited by 827 · see citing works

Inappropriate Activation of the TSC/Rheb/mTOR/S6K Cassette Induces IRS1/2 Depletion, Insulin Resistance, and Cell Survival Deficiencies

Shah, O. J., Wang, Z., & Hunter, T. R. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.026 · Cited by 800 · see citing works

Drosophila S6 kinase: a regulator of cell size.

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

Nobukuni, T., Joaquin, M., Roccio, M., Dann, S. G., Kim, S. Y., Gulati, P., Byfield, M. P., Backer, J., Natt, F., Bos, J. L., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506925102 · Cited by 753 · see citing works

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

Roux, P. P., Ballif, B. A., Anjum, R., Gygi, S. P., & Blenis, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405659101 · Cited by 750 · see citing works

Tsc tumour suppressor proteins antagonize amino-acid–TOR signalling

Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R. S., Ru, B., & Pan, D. (2002) · Nature Cell Biology · doi:10.1038/ncb847 · Cited by 719 · see citing works

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

DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W. (2008) · Genes &amp; Development · doi:10.1101/gad.1617608 · Cited by 710 · see citing works

A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells

Kwiatkowski, D. J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.525 · Cited by 667 · see citing works

Rheb promotes cell growth as a component of the insulin/TOR signalling network

Saucedo, L. J., Gao, X., Chiarelli, D. A., Li, L., Pan, D., & Edgar, B. A. (2003) · Nature Cell Biology · doi:10.1038/ncb996 · Cited by 658 · see citing works

Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis

Carsillo, T., Astrinidis, A., & Henske, E. P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.11.6085 · Cited by 648 · see citing works

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

Lee, D., Kuo, H.-P., Chen, C., Hsu, J.-M., Chou, C., Wei, Y., Sun, H., Li, L., Ping, B., Huang, W., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.058 · Cited by 639 · see citing works

Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase‐1 and p70 S6 kinase

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Rapamycin causes regression of astrocytomas in tuberous sclerosis complex

Franz, D. N., Leonard, J. M., Tudor, C., Chuck, G., Caré, M. M., Sethuraman, G., Dinopoulos, A., Thomas, G., & Crone, K. R. (2006) · Annals of Neurology · doi:10.1002/ana.20784 · Cited by 614 · see citing works

Hypoxia-induced energy stress regulates mRNA translation and cell growth

Liu, L., Cash, T. P., Jones, R. G., Keith, B., Thompson, C. B., & Simon, M. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.010 · Cited by 607 · see citing works

The NF1 tumor suppressor critically regulates TSC2 and mTOR

Johannessen, C. M., Reczek, E. E., James, M. F., Brems, H., Legius, E., & Cichowski, K. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503224102 · Cited by 605 · see citing works

An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten +/− mice

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Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products

van Slegtenhorst, M. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.6.1053 · Cited by 565 · see citing works

The Drosophila Tuberous Sclerosis Complex Gene Homologs Restrict Cell Growth and Cell Proliferation

Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E., & Hariharan, I. K. (2001) · Cell · doi:10.1016/s0092-8674(01)00332-4 · Cited by 542 · see citing works

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

Zhang, H., Cicchetti, G., Onda, H., Koon, H. B., Asrican, K., Bajraszewski, N., Vázquez, F., Carpenter, C. L., & Kwiatkowski, D. J. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17222 · Cited by 538 · see citing works

Rheb is an essential regulator of S6K in controlling cell growth in Drosophila

Stocker, H., Radimerski, T., Schindelholz, B., Wittwer, F., Belawat, P., Daram, P., Breuer, S., Thomas, G., & Hafen, E. (2003) · Nature Cell Biology · doi:10.1038/ncb995 · Cited by 530 · see citing works

hVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase

Byfield, M. P., Murray, J. T., & Backer, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507201200 · Cited by 526 · see citing works

Drosophila Tsc1 Functions with Tsc2 to Antagonize Insulin Signaling in Regulating Cell Growth, Cell Proliferation, and Organ Size

Potter, C. J., Huang, H., & Xu, T. (2001) · Cell · doi:10.1016/s0092-8674(01)00333-6 · Cited by 522 · see citing works

The TSC1-TSC2 Complex Is Required for Proper Activation of mTOR Complex 2

Huang, J., Dibble, C. C., Matsuzaki, M., & Manning, B. D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00289-08 · Cited by 504 · see citing works

TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.Preprint

Gao, X., & Pan, D. (2001) · Genes & Development · doi:10.1101/gad.901101 · Cited by 484 · see citing works

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

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Balancing Akt with S6K

Manning, B. D. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200408161 · Cited by 476 · see citing works

A Novel Hypoxia-inducible Factor-independent Hypoxic Response Regulating Mammalian Target of Rapamycin and Its Targets

Arsham, A. M., Howell, J. J., & Simon, M. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212770200 · Cited by 463 · see citing works

Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1

Sofer, A., Lei, K., Johannessen, C. M., & Ellisen, L. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5834-5845.2005 · Cited by 449 · see citing works

The principal target of rapamycin‐induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.

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Tuberin Regulates p70 S6 Kinase Activation and Ribosomal Protein S6 Phosphorylation

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Rheb Activates mTOR by Antagonizing Its Endogenous Inhibitor, FKBP38

Bai, X., Ma, D., Liu, A., Shen, X., Wang, Q. J., Liu, Y., & Jiang, Y. (2007) · Science · doi:10.1126/science.1147379 · Cited by 382 · see citing works

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

Zhang, H., Bajraszewski, N., Wu, E., Wang, H., Moseman, A. P., Dabora, S. L., Griffin, J. D., & Kwiatkowski, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28984 · Cited by 382 · see citing works

Rheb Binds Tuberous Sclerosis Complex 2 (TSC2) and Promotes S6 Kinase Activation in a Rapamycin- and Farnesylation-dependent Manner

Castro, A. F., Rebhun, J. F., Clark, G. J., & Quilliam, L. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300226200 · Cited by 381 · see citing works

Akt Activation Promotes Degradation of Tuberin and FOXO3a via the Proteasome

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Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning

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Identification of Tuberin, the Tuberous Sclerosis-2 Product. TUBERIN POSSESSES SPECIFIC Rap1GAP ACTIVITY

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

Smith, E. M., FINN, S. G., Tee, A. R., Browne, G. J., & Proud, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414499200 · Cited by 354 · see citing works

Rheb Binding to Mammalian Target of Rapamycin (mTOR) Is Regulated by Amino Acid Sufficiency

Long, X., Ortiz-Vega, S., Lin, Y., & Avruch, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500169200 · Cited by 349 · see citing works

The Tuberous Sclerosis 2 Gene Product, Tuberin, Functions as a Rab5 GTPase Activating Protein (GAP) in Modulating Endocytosis

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Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease

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S6K1 Regulates GSK3 under Conditions of mTOR-Dependent Feedback Inhibition of Akt

Zhang, H. H., Lipovsky, A. I., Dibble, C. C., Şahin, M., & Manning, B. D. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.09.019 · Cited by 309 · see citing works

Proteomic Analysis Reveals Hyperactivation of the Mammalian Target of Rapamycin Pathway in Neurofibromatosis 1–Associated Human and Mouse Brain Tumors

Dasgupta, B., Yi, Y., Chen, D. Y., Weber, J. D., & Gutmann, D. H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4058 · Cited by 308 · see citing works

A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt

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Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase

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

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Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors.

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Genetic control of cell size.

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

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New roles for the LKB1→AMPK pathway

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The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination

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