Cited by 1,237PI3K/AKT/mTOR signaling in cancerTuberous Sclerosis Complex ResearchHippo pathway signaling and YAP/TAZ

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

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Huang, Jingxiang, Manning, Brendan D.·2008·Biochemical Journal

DOI 10.1042/bj20080281PMC PMC2735030

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Abstract

TSC1 and TSC2 are the tumour-suppressor genes mutated in the tumour syndrome TSC (tuberous sclerosis complex). Their gene products form a complex that has become the focus of many signal transduction researchers. The TSC1–TSC2 (hamartin–tuberin) complex, through its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain), is a critical negative regulator of mTORC1 (mammalian target of rapamycin complex 1). As mTORC1 activity controls anabolic processes to promote cell growth, it is exquisitely sensitive to alterations in cell growth conditions. Through numerous phosphorylation events, the TSC1–TSC2 complex has emerged as the sensor and integrator of these growth conditions, relaying signals from diverse cellular pathways to properly modulate mTORC1 activity. In the present review we focus on the molecular details of TSC1–TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.

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1 retracted

Phosphatidylinositol 3-Kinase/Akt Pathway Regulates Tuberous Sclerosis Tumor Suppressor Complex by Phosphorylation of Tuberin
Dan, H. C., Sun, M., Yang, L., Feldman, R. I., Sui, X.-M., Ou, C. C., Nellist, M. D., Yeung, R. S. W., Halley, D. J. J., Nicosia, S. V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205838200 · Cited by 370
Retracted
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
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Self-citation
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
Upstream and downstream of mTOR
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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
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
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Background
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“TSC1 and TSC2 are the tumor-suppressor genes mutated in the tumor syndrome TSC (tuberous sclerosis complex) and their gene products form a complex (TSC1–TSC2) that integrates signals upstream of mTOR signaling pathway through its GAP activity towards the small Gprotein Rheb [42].”
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Background
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Background
mTOR signaling: RAG GTPases transmit the amino acid signal
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Background
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Background
Tnfaip8 l1/Oxi‐β binds to FBXW 5, increasing autophagy through activation of TSC 2 in a Parkinson's disease model
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Background
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Background
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Background
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Background
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Background
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“activity of the small GTPase Rheb [42–45].”
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“Therefore, our results indicate that Sestrin2 not only suppresses mTORC1 but concurrently activates mTORC2, a finding that aligns with other work indicating that tuberous sclerosis complex and AMPK inhibit mTORC1 but activate mTORC2 (32, 36, 37).”
Result
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“As a result, Akt-mediated repression of TSC sustains RHEB-GTP, thereby promoting mTORC1 activity.”
BackgroundInfluential
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BackgroundInfluential
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“Based on the knowledge on mammalian counterparts, this likely results in acute sequestration of TSC from the lysosomal membrane to the cytoplasm by 14-3-3 chaperone proteins [129] (reviewed in [123]).”
Background
TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity
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“…formation of a functional TSC1/TSC2 complex resulting in constitutive activation of mTORC1 and phosphorylation of its downstream targets S6K and 4E-BP1, with net effects of abnormal translational activation leading to cell growth and proliferation (Guertin & Sabatini, 2007; Huang & Manning, 2008).”
Background
Critical Role of the Tumor Suppressor Tuberous Sclerosis Complex 1 in Dendritic Cell Activation of CD4 T Cells by Promoting MHC Class II Expression via IRF4 and CIITA
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“TSC1 stabilizes TSC2 by preventing ubiquitin-mediated degradation (25).”
Background
Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference
Şahin, M., Henske, E. P., Manning, B. D., Ess, K. C., Bissler, J. J., Klann, E., Kwiatkowski, D. J., Roberds, S. L., Silva, A. J., Hillaire‐Clarke, C. S., et al. (2016) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2016.03.015 · Cited by 57
Self-citation
Signal transduction pathways and resistance to targeted therapies in glioma
Tomiyama, A., & Ichimura, K. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.01.004 · Cited by 54
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
Hildebrandt, M. A. T., Lippman, S. M., Etzel, C. J., Kim, E., Lee, J. J., Khuri, F. R., Spitz, M. R., Lotan, R., Hong, W. K., & Wu, X. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3271 · Cited by 53
“TSC1 plays amajor role in regulating the PI3K/PTEN/AKT/mTOR pathway through the activation/suppression of mTOR activity (11, 12), and loss of TSC1 function results in uncontrolled cell growth and proliferation (13).”
Epigenetic regulation of autophagy-related genes: Implications for neurodevelopmental disorders
Lewerissa, E., Kasri, N. N., & Linda, K. (2023) · Autophagy · doi:10.1080/15548627.2023.2250217 · Cited by 56
“Given that TSC2 inhibits MTOR at the lysosomes in response to nutrient short-age [43], one can hypothesize that increased TSC2 leads to overactivation of autophagy potentially affecting neuronal development in EZH2-deficient cells.”
Background
Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin
Malhowski, A. J., Hira, H., Bashiruddin, S., Warburton, R. R., Goto, J., Robert, B., Kwiatkowski, D. J., & Finlay, G. A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq570 · Cited by 51
Regulation of autophagy and EMT by the interplay between p53 and RAS during cancer progression (Review)
Zhang, X., Cheng, Q., Yin, H., & Yang, G. S. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.4025 · Cited by 55
Uncoupling effects of estrogen receptor α on LKB1/AMPK interaction upon adiponectin exposure in breast cancer
Mauro, L., Naimo, G. D., Gelsomino, L., Malivindi, R., Bruno, L., PELLEGRINO, M. A., Tarallo, R., Memoli, D., Weisz, A., Panno, M. L., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201701315r · Cited by 54
“Activation of PI3K/Akt removes the inhibitory effect of the AMPK/TSC2 axis on Rebdetermining mTOR activation and consequently cell survival and growth (17).”
BackgroundInfluential
The Ion Transporter NKCC1 Links Cell Volume to Cell Mass Regulation by Suppressing mTORC1
Demian, W. L., Persaud, A. K., Jiang, C., Coyaud, É., Liu, S., Kapùs, A., Kafri, R., Raught, B., & Rotin, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.034 · Cited by 54
Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation
Charitou, T., Srihari, S., Lynn, M. A., Jarboui, M. A., Fasterius, E., Moldovan, M. V., Shirasawa, S., Tsunoda, T., Ueffing, M., Xie, J., et al. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0477-7 · Cited by 56
Dietary Polyphenols in Metabolic and Neurodegenerative Diseases: Molecular Targets in Autophagy and Biological Effects
García-Aguilar, A., Palomino, O. M., Benito, M., & Guillén, C. (2021) · Antioxidants · doi:10.3390/antiox10020142 · Cited by 54
“The TSC complex is an essential inhibitor of mTORC1 activity through the activation of its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain) [48].”
Background
Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex
Hoogeveen‐Westerveld, M., Ekong, R., Povey, S., Karbassi, I., Batish, S. D., den Dunnen, J. T., van Eeghen, A. M., Thiele, E. A., Mayer, K., Dies, K. A., et al. (2011) · Human Mutation · doi:10.1002/humu.22007 · Cited by 53
Elevated PI3K signaling drives multiple Breast Cancer subtypes
Adams, J. R., Schachter, N. F., Liu, J. C., Zacksenhaus, E., & Egan, S. E. (2011) · Oncotarget · doi:10.18632/oncotarget.285 · Cited by 51
“TORC1 is also regulated by Rag-family GTPases that respond to amino acid levels, AMP kinase that is regulated by the AMP:ATP ratio as a readout of cellular energy levels, as well as by the Rac GTPase that functions downstream of growth factor signaling [21].”
Background
The mechanical activation of mTOR signaling: an emerging role for late endosome/lysosomal targeting
Jacobs, B. L., Goodman, C. A., & Hornberger, T. A. (2013) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-013-9367-4 · Cited by 56
“For example, growth factor induced changes in the phosphorylation of TSC2 do not alter TSC2’s GAP activity when measured in vitro (Cai et al. 2006; Huang and Manning 2008).”
Evolution of the TSC1/TSC2-TOR Signaling Pathway
Serfontein, J., Nisbet, R. E. R., Howe, C. J., & de Vries, P. J. (2010) · Science Signaling · doi:10.1126/scisignal.2000803 · Cited by 52
Tuberous sclerosis complex: linking cancer to metabolism
Mieulet, V., & Lamb, R. F. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.05.001 · Cited by 52
Rapamycin enhances eIF4E phosphorylation by activating MAP kinase‐interacting kinase 2a (Mnk2a)
Stead, R., & Proud, C. G. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.06.045 · Cited by 53
“mTORC1 is activated downstream of signaling pathways such as the ERK MAP kinase and protein kinase B (Akt) (reviewed [7,8]), which include components that become oncogenic (e.”
Background
PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis
Akundi, R. S., Zhi, L., & Büeler, H. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.08.034 · Cited by 52
Genetic Mechanisms of ADPKD
Kim, D. Y., & Park, J. H. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-2041-4_2 · Cited by 50
The TSC Complex-mTORC1 Axis: From Lysosomes to Stress Granules and Back
Rehbein, U., Prentzell, M. T., Sandoval, M. C., Heberle, A. M., Henske, E. P., Opitz, C. A., & Thedieck, K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.751892 · Cited by 52
“GTP-bound RHEB activates mTORC1, and the TSC complex suppresses mTORC1 upon growth factor shortage, nutrient deprivation, and other stresses (Huang and Manning, 2008; Plescher et al., 2015; Demetriades et al., 2016; Fernandes and Demetriades, 2021).”
BackgroundInfluential
Autophagy: from basic science to clinical application
Limbergen, J. V., Stevens, C., Nimmo, E., Wilson, D., & Satsangi, J. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.20 · Cited by 53
Tuberous sclerosis complex
Peron, A., & Northrup, H. (2018) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31657 · Cited by 50
The Serine Protease HtrA1 Specifically Interacts and Degrades the Tuberous Sclerosis Complex 2 Protein
Campioni, M., Severino, A., Manente, L., Tuduce, I. L., Toldo, S. A., Caraglia, M., Crispi, S., Ehrmann, M., He, X., Maguire, J. L., et al. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0473 · Cited by 50
“For the mapping experiment, 1μg of plasmid encoding for the different truncated expression constructs of TSC2 (TSC2[1-607], TSC2[607-1099] and TSC2[1099-1807]) was used for in vitro translation as described above.”
BackgroundMethod
Everolimus for the Treatment of Tuberous Sclerosis Complex–Related Cardiac Rhabdomyomas in Pediatric Patients
Dahdah, N. (2017) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2017.06.076 · Cited by 50
Neural progenitors derived from Tuberous Sclerosis Complex patients exhibit attenuated PI3K/AKT signaling and delayed neuronal differentiation
Zucco, A. J., Pozzo, V. D., Afinogenova, A., Hart, R. P., Devinsky, O., & D’Arcangelo, G. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.08.004 · Cited by 48
“The TSC1/TSC2 complex is a key regulator of mTORC1 activity in response to growth factor signaling, and mTORC1 upregulation has been observed in numerous homozygous animal or cellular models of TSC (Goto et al., 2011; Huang and Manning, 2008; Inoki et al., 2003; Magri et al., 2011; Meikle et al., 2007).”
Angiotensin II-Regulated Autophagy Is Required for Vascular Smooth Muscle Cell Hypertrophy
Mondaca‐Ruff, D., Riquelme, J. A., Quiroga, C., Norambuena‐Soto, I., Sanhueza‐Olivares, F., Villar-Fincheira, P., Hernández‐Díaz, T., Cancino-Arenas, N., Martín, A. S., Garcı́a, L., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01553 · Cited by 52
“Phosphorylation of Thr1462 inhibits TSC2 activity and induces mTOR activation (Huang and Manning, 2008).”
Background
The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions
Man, A., Scipio, M. D., Grewal, S., Suk, Y., Trinari, E., Ejaz, R., & Whitney, R. (2024) · Genes · doi:10.3390/genes15030332 · Cited by 55
Insulin like growth factor‐1‐induced phosphorylation and altered distribution of tuberous sclerosis complex (TSC)1/TSC2 in C2C12 myotubes
Miyazaki, M., McCarthy, J. J., & Esser, K. A. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07635.x · Cited by 50
Soy Isoflavones Regulate Lipid Metabolism through an AKT/mTORC1 Pathway in Diet-Induced Obesity (DIO) Male Rats
Huang, C., Pang, D., Luo, Q., Chen, X., Gao, Q., Shi, L., Liu, W., Zou, Y., Li, L., & Chen, Z. (2016) · Molecules · doi:10.3390/molecules21050586 · Cited by 49
“myriad of cellular processes, such as protein synthesis and autophagy [12].”
Background
Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast
Kim, J., Yu, J. H., Nam, S. J., Kim, S. W., Lee, S. K., Park, W., Noh, D., Nam, D., Park, Y. H., Han, W., et al. (2017) · Translational Oncology · doi:10.1016/j.tranon.2017.10.002 · Cited by 49
“PARP inhibitor targeting BRCA2 and mTOR/AKT inhibitor for TSC1 would be potential target agents for the treatment of metastatic MPTs [24,25].”
Background
Activation of Calcium-Sensing Receptor increases intracellular calcium and decreases cAMP and mTOR in PKD1 deficient cells
Mise, A. D., Tamma, G., Ranieri, M., Centrone, M., van den Heuvel, L. P., Mekahli, D., Levtchenko, E. N., & Valenti, G. (2018) · Scientific Reports · doi:10.1038/s41598-018-23732-5 · Cited by 48
Inhibition of the GTPase Rac1 Mediates the Antimigratory Effects of Metformin in Prostate Cancer Cells
Dirat, B., Ader, I., Golzio, M., Massa, F., Mettouchi, A., Laurent, K., Larbret, F., Malavaud, B. A., Cormont, M., Lemichez, E., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0102 · Cited by 48
“The PIP3 phosphatidylinositol (3,4,5)-triphosphate–dependent Rac exchanger 1 (P-Rex1), a Rac-selective GEF, plays an important role in actin remodeling and cell migration.”
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48
“Shut-down of the growthfacilitating mTORC1 pathway, however, promotes the activity of the unc-51 like autophagy activating kinase (ULK1/2) initiation complex, which launches autophagosome maturation and the cellular purging of waste products, such as Aß, Tau or αsynuclein (Huang and Manning, 2008; Ma and Blenis, 2009;…”
Background
AMP‐activated protein kinase counteracts brain‐derived neurotrophic factor‐induced mammalian target of rapamycin complex 1 signaling in neurons
Ishizuka, Y., Kakiya, N., Witters, L. A., Oshiro, N., Shirao, T., Nawa, H., & Takei, N. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12362 · Cited by 46
Sirolimus Decreases Circulating Lymphangioleiomyomatosis Cells in Patients With Lymphangioleiomyomatosis
Cai, X., Pacheco–Rodriguez, G., Haughey, M., Samsel, L., Xu, S., Wu, H.-P., McCoy, J. P., Stylianou, M. P., Darling, T. N., & Moss, J. (2013) · CHEST Journal · doi:10.1378/chest.13-1071 · Cited by 47
PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex
Alves, M. M., Fuhler, G. M., Queiroz, K. C. S., Scholma, J., Goorden, S. M. I., Anink, J. J., Spek, C. A., Hoogeveen‐Westerveld, M., Bruno, M. J., Nellist, M. D., et al. (2015) · Scientific Reports · doi:10.1038/srep14534 · Cited by 47
Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling
Lee, Y., Kim, S. G., Lee, B., Zhang, Y., Kim, Y., Kim, S., Kim, E., Kang, H., & Han, K. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00201 · Cited by 47
“The heterodimeric complex of tuberous sclerosis 1 (TSC1) and TSC2 is a critical upstream regulator of mTORC1 that functions as a guanosine triphosphatase (GTPase)-activating protein (GAP) for the small GTPase Ras homolog enriched in brain (Rheb; Huang and Manning, 2008).”
Background
The mTOR pathway: Implications for DNA replication
Lamm, N., Rogers, S., & Cesare, A. J. (2019) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2019.04.002 · Cited by 51
Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis
Hoepner, R., Bagnoud, M., Pistor, M., Salmen, A., Briner, M., Synn, H., Schrewe, L., Guse, K., Ahmadi, F., Demir, S., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02018-8 · Cited by 47
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation
Alsaqati, M., Heine, V. M., & Harwood, A. J. (2020) · Molecular Autism · doi:10.1186/s13229-020-00391-w · Cited by 47
“The mTORC1 pathway plays key roles in multiple cellular processes, such as cell growth and division, autophagy and transcription [4, 5].”
Background
The role of metabolic ecosystem in cancer progression — metabolic plasticity and mTOR hyperactivity in tumor tissues
Sebestyén, A. R., Dankó, T., Sztankovics, D., Moldvai, D., Raffay, R. E., Cervi, C., Krencz, I., Zsiros, V., Jeney, A., & Petővári, G. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-10006-2 · Cited by 48
p53-regulated autophagy is controlled by glycolysis and determines cell fate
Duan, L., Perez, R. E., Davaadelger, B., Dedkova, E. N., Blatter, L. A., & Maki, C. G. (2015) · Oncotarget · doi:10.18632/oncotarget.5218 · Cited by 46
“Activated AMPK then phosphorylates TSC2, which inhibits mTORC1 [20], or directly phosphorylates the mTORC1 binding partner Raptor to inhibit mTOCR1 activity [21].”
Background
The Molecular Biology of Renal Cell Carcinoma
O’Keefe, S. J., Nathanson, K. L., & Rathmell, W. K. (2013) · Seminars in Oncology · doi:10.1053/j.seminoncol.2013.05.006 · Cited by 48
PRAS40 acts as a nodal regulator of high glucose‐induced TORC1 activation in glomerular mesangial cell hypertrophy
Dey, N., Ghosh‐Choudhury, N., Das, F., Li, X., Venkatesan, B. A., Barnes, J. L., Kasinath, B. S., & Choudhury, G. G. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22186 · Cited by 46
PPARγ activation attenuates glucose intolerance induced by mTOR inhibition with rapamycin in rats
Festuccia, W. T., Blanchard, P.-G., Belchior, T., Chimin, P., Paschoal, V. A., Magdalon, J., Hirabara, S. M., Simões, D., St‐Pierre, P., Carpinelli, Â. R., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00683.2013 · Cited by 47
“Indeed, chronic mTORC1 overactivation is a major phenotype found in pathological conditions such as tuberous sclerosis complex disease (17), many types of cancer (29), obesity, and type 2 diabetes (18, 40).”
Background
Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases
Chia, K. H., Fukuda, T., Sofyantoro, F., Matsuda, T., Amai, T., & Shiozaki, K. (2017) · eLife · doi:10.7554/elife.30880 · Cited by 54
“Because deregulated mTORC1 activation is implicated in cancerous cell proliferation and neurologi- cal disorders including epilepsy (Huang and Manning, 2008; Baldassari et al., 2016), the molecular mechanisms that negatively regulate mTORC1 warrant further investigation.”
Background

Authors: Huang, J., & Manning, B. D.
Affiliations: Harvard University (US)
ORCID: Huang, Jingxiang
Manning, Brendan D.
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 2008-05-14
Volume: 412
Issue: 2
Pages: 179-190
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj20080281
PMC: PMC2735030
OpenAlex: W1993431258
Cited by: 1,237
References: 133
Citations by year: 2026: 26 · 2025: 58 · 2024: 53 · 2023: 62 · 2022: 77 · 2021: 83 · 2020: 77 · 2019: 69 · 2018: 74 · 2017: 79 · 2016: 68 · 2015: 82 · 2014: 70 · 2013: 72 · 2012: 73
FWCI: 5.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Biochemical Journal (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA122617, P01CA120964)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Genetics (clinical) › Tuberous Sclerosis Complex Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords: TSC1/TSC2 complex, hamartin, tuberin, tuberous sclerosis complex, Rheb, GTPase-activating protein, mTORC1, cell growth regulation, signal transduction, phosphorylation, anabolic processes, tumor suppressor
MeSH terms: Ras Homolog Enriched in Brain Protein, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Amino Acid Sequence, Animals, Cell Cycle, Humans, Insulin, Insulin-Like Growth Factor I, Molecular Sequence Data, Neuropeptides, Protein Kinases, Transcription Factors, Signal Transduction, Genes, Tumor Suppressor, Sequence Alignment, Ribosomal Protein S6 Kinases, Monomeric GTP-Binding Proteins, Tumor Suppressor Proteins, Intercellular Signaling Peptides and Proteins, Cell Growth Processes, TOR Serine-Threonine Kinases

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

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