The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Open accessAbstract
Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2 . The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“mTORC1-TFEB signaling governs lysosomal biogenesis (Laplante and Sabatini 2012), (Inoki et al. 2003), (Tee et al. 2003), (Sardiello et al. 2009), (Settembre et al. 2012), (Settembre et al. 2013), (Sardiello et al. 2009), (Martina et al. 2014), and TFEB targets include several genes, including MCOLN1 (Nnah et al. 2019).”
From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Inoki et al. 2003
Experimental — accuracy not yet measuredIn the citing paper
“The TSC complex (TSCC) acts as a GTPase activating protein (GAP) for Rheb, employing a GAP domain within the TSC2 subunit”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Inoki et al., 2003
In the citing paper
“Activation of mTORC1 by Rheb downstream of growth-factor signaling (Inoki et al. 2003), (Tee et al. 2003), controls lysosomal and autophagosome biogenesis via TFEB and the CLEAR gene network (Sardiello et al. 2009), (Settembre et al. 2012).”
From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Inoki et al. 2003
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Self-citationeIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of Translation
Gingras, A., Raught, B., & Sonenberg, N. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.913 · Cited by 2,103
Identification and characterization of the tuberous sclerosis gene on chromosome 16
(1993) · Cell · doi:10.1016/0092-8674(93)90618-z · Cited by 1,645
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
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370
A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic Mutants
Trahey, M., & McCormick, F. (1987) · Science · doi:10.1126/science.2821624 · Cited by 1,211
FUNCTION AND REGULATION OF RAS
Lowy, D. R., & Willumsen, B. M. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.004223 · Cited by 1,164
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055
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
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
Research works printed but not linked: 1
- 2002, Cancer Res., 62, 5645
Cited by
Sorted by citations
Items 801–900 of 1,009
Differential control of muscle mass in type 1 and type 2 diabetes mellitus
Sala, D., & Antonio Zorzano, A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1954-7 · Cited by 45
Gordon, B. S., Steiner, J. L., Lang, C. H., Jefferson, L. S., & Kimball, S. R. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00250.2014 · Cited by 47
Integration of signals generated by nutrients, hormones, and exercise in skeletal muscle.
Kimball, S. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.068387 · Cited by 46
To eat, or NOt to eat: S ‐nitrosylation signaling in autophagy
Montagna, C., Rizza, S., Maiani, E., Piredda, L., Filomeni, G., & Cecconi, F. (2016) · The FEBS Journal · doi:10.1111/febs.13736 · Cited by 42
Huynh, L., Kusnadi, A., Park, S. H., Murata, K., Park‐Min, K., & Ivashkiv, L. B. (2016) · Scientific Reports · doi:10.1038/srep31959 · Cited by 45
Tuberous sclerosis complex: From molecular biology to novel therapeutic approaches
Switon, K., Kotulska, K., Janusz, A., Zmorzyńska, J., & Jaworski, J. (2016) · IUBMB Life · doi:10.1002/iub.1579 · Cited by 44
Hyttinen, J. M. T., Petrovski, G., Salminen, A., & Kaarniranta, K. (2011) · Rejuvenation Research · doi:10.1089/rej.2011.1220 · Cited by 44
Kwak, D., Choi, S., Jeong, H., Jang, J., Lee, Y., Jeon, H., Lee, M. N., Noh, J., Cho, K., Yoo, J. S., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.326538 · Cited by 44
Hong‐Brown, L. Q., Brown, C. R., Kazi, A. A., Navaratnarajah, M., & Lang, C. H. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00407.2011 · Cited by 44
Mafi, S., Ahmadi, E., Meehan, E. V., Chiari, C. C., Mansoori, B., Sadeghi, H., Milani, S., Jafarinia, M., Taeb, S., Bashmagh, B. M., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-3032 · Cited by 43
Wang, G. Y., Qin, S. L., Zheng, Y. N., Geng, H., Chen, L., Yao, J. H., & Deng, L. (2023) · Animal nutrition · doi:10.1016/j.aninu.2023.07.001 · Cited by 48
Calamaras, T. D., Lee, C., Lan, F., Ido, Y., Siwik, D. A., & Colucci, W. S. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.01.007 · Cited by 43
Key mediators of intracellular amino acids signaling to mTORC1 activation
Duan, Y., Li, F., Tan, K., Liu, H., Li, Y., Liu, Y., Kong, X., Tang, Y., Wu, G., & Yin, Y. (2015) · Amino Acids · doi:10.1007/s00726-015-1937-x · Cited by 43
Self-citationNakhaei‐Rad, S., Haghighi, F., Nouri, P., Adariani, S. R., Lissy, J., Jasemi, N. S. K., Dvorský, R., & Ahmadian, M. R. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1431605 · Cited by 44
Sato, T., Umetsu, A., & Tamanoi, F. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)38021-x · Cited by 43
Jones, K. A., Jiang, X., Yamamoto, Y., & Yeung, R. S. W. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.01.022 · Cited by 43
Parkhitko, A. A., Favorova, O. O., Khabibullin, D., Anisimov, V. N., & Henske, E. P. (2014) · Biochemistry (Moscow) · doi:10.1134/s0006297914020023 · Cited by 44
The mTOR Pathway in Breast Cancer
Hynes, N. E., & Boulay, A. (2006) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-006-9012-6 · Cited by 46
Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex
Sundberg, M., & Şahin, M. (2015) · Journal of Child Neurology · doi:10.1177/0883073815600870 · Cited by 45
Babcock, J. T., Nguyen, H., He, Y., Hendricks, J. W., Wek, R. C., & Quilliam, L. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.431056 · Cited by 43
Yasuda, S., Sugiura, H., Katsurabayashi, S., Shimada, T., Tanaka, H., Takasaki, K., Iwasaki, K., Kobayashi, T., Hino, O., & Yamagata, K. (2014) · Scientific Reports · doi:10.1038/srep05155 · Cited by 43
A Rab10:RalA G protein cascade regulates insulin-stimulated glucose uptake in adipocytes
Karunanithi, S., Xiong, T., Uhm, M., Leto, D. E., Sun, J., Chen, X., & Saltiel, A. R. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-06-1060 · Cited by 42
Martín, R., Portantier, M., Chica, N., Nyquist-Andersen, M., Mata, J., & López‐Avilés, S. (2016) · Current Biology · doi:10.1016/j.cub.2016.11.037 · Cited by 43
Self-Eating for Muscle Fitness: Autophagy in the Control of Energy Metabolism
Sebastián, D., & Antonio Zorzano, A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.030 · Cited by 43
TSC1 Sets the Rate of Ribosome Export and Protein Synthesis through Nucleophosmin Translation
Pelletier, C. L., Maggi, L. B., Brady, S. N., Scheidenhelm, D. K., Gutmann, D. H., & Weber, J. D. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2875 · Cited by 42
Clinical activity of mammalian target of rapamycin inhibitors in solid tumors
Alvarado, Y., Mita, M. M., Vemulapalli, S., Mahalingam, D., & Mita, A. C. (2011) · Targeted Oncology · doi:10.1007/s11523-011-0178-5 · Cited by 41
GPCR signalling to the translation machinery
Musnier, A., Blanchot, B., Reiter, É., & Crépieux, P. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.10.012 · Cited by 41
Liu, Y., Kelamangalath, L., Kim, H., Han, S. B., Tang, X., Zhai, J., Hong, J. W., Lin, S., Son, Y., & Smith, G. M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.05.021 · Cited by 41
Chi-Sabins, N., Chornoguz, O., Leander, K. R., Kaplan, F. M., Carter, R., Kinder, M., Bachman, K. E., Verona, R. I., Shen, S., Bhargava, V., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701030 · Cited by 41
Wang, L., Du, J.-L., Zhao, F., Chen, Z., Chang, J., Qin, F., Wang, Z., Wang, F., Chen, X., & Chen, N. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.12.046 · Cited by 41
Hu, M., Chen, X., Ma, L., Ma, Y., Li, Y., Song, H.-H., Xu, J., Zhou, L., Li, X., Jiang, Y., et al. (2019) · Journal of Cancer · doi:10.7150/jca.28299 · Cited by 43
Self-citationIron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways
Shang, C., Zhou, H., Liu, W., Shen, T., Luo, Y., & Huang, S. (2020) · Oncogene · doi:10.1038/s41388-020-1366-5 · Cited by 43
Enzyme Replacement Therapy Can Reverse Pathogenic Cascade in Pompe Disease
Meena, N. K., Ralston, E., Raben, N., & Puertollano, R. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.05.026 · Cited by 43
Rheb G-Proteins and the Activation of mTORC1
(2010) · The Enzymes · doi:10.1016/s1874-6047(10)27003-8 · Cited by 41
Novel insulin-elicited phosphoproteins in adipocytes
Gridley, S., Lane, W. S., Garner, C. W., & Lienhard, G. E. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.05.013 · Cited by 41
Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness
Nowosad, A., & Besson, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042290 · Cited by 39
Branched-Chain Amino Acids in Liver Diseases: Complexity and Controversy
Zhang, Y., Zhan, L., Zhang, L., Shi, Q., & Li, L. (2024) · Nutrients · doi:10.3390/nu16121875 · Cited by 43
Fouqué, A., Delalande, O., Jean, M., Castellano, R., Josselin, E., Malleter, M., Shoji, K. F., Mac, D. H., Rampanarivo, H., Collette, Y., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00991 · Cited by 40
Targeting phosphatidylinositol 3 kinase (PI3K)-Akt beyond rapalogs
Ogita, S., & LoRusso, P. M. (2011) · Targeted Oncology · doi:10.1007/s11523-011-0176-7 · Cited by 40
mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation
Asrani, K. V., Sood, A., Torres, A., Georgess, D., Phatak, P., Kaur, H. B., Dubin, A., Talbot, C. C., Elhelu, L., Ewald, A. J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92893 · Cited by 41
New insights in lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis
Torre, O., Elia, D., Caminati, A., & Harari, S. A. (2017) · European Respiratory Review · doi:10.1183/16000617.0042-2017 · Cited by 40
miR-185 Inhibits Fibrogenic Activation of Hepatic Stellate Cells and Prevents Liver Fibrosis
Zhou, L., Liu, S., Han, M., Ma, Y., Feng, S., Zhao, J., Lu, H., Yuan, X., & Cheng, J. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.11.010 · Cited by 40
Nayman, A. H., Siginc, H. I., Zemheri, E. I., Yencilek, F., Yildirim, A., & Telci, D. (2019) · Journal of Cancer · doi:10.7150/jca.29192 · Cited by 39
Coordination of Rheb lysosomal membrane interactions with mTORC1 activation
Angarola, B. L., & Ferguson, S. M. (2020) · F1000Research · doi:10.12688/f1000research.22367.1 · Cited by 40
Structural Insights into TOR Signaling
Tafur, L., Kefauver, J. M., & Loewith, R. (2020) · Genes · doi:10.3390/genes11080885 · Cited by 42
The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health
Mozolewski, P., Jeziorek, M., Schuster, C., Bading, H., Frost, B. E., & Dobrowolski, R. (2021) · Journal of Cell Science · doi:10.1242/jcs.254904 · Cited by 39
The regulation of healthspan and lifespan by dietary amino acids
Babygirija, R., & Lamming, D. W. (2021) · Translational Medicine of Aging · doi:10.1016/j.tma.2021.05.001 · Cited by 43
Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex
Karalis, V., Caval-Holme, F., & Bateup, H. S. (2022) · Nature Communications · doi:10.1038/s41467-022-31961-6 · Cited by 40
Analysis of the regulatory motifs in eukaryotic initiation factor 4E‐binding protein 1
Lee, V. H.-Y., Healy, T. M., Fonseca, B. D., Hayashi, A. A., & Proud, C. G. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06372.x · Cited by 41
RRP22 Is a Farnesylated, Nucleolar, Ras-Related Protein with Tumor Suppressor Potential
Elam, C. A., Hesson, L. B., Vos, M. D., Eckfeld, K., Ellis, C. A., Bell, A., Krex, D., Birrer, M. J., Latif, F., & Clark, G. J. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-0749 · Cited by 40
Lee, S.-J., Feldman, R., & O’Farrell, P. H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-03-0265 · Cited by 36
Nemazanyy, I., Panasyuk, G., Zhyvoloup, A., Panayotou, G., Gout, I. T., & Filonenko, V. V. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.10.091 · Cited by 41
Jain, P., & Bhalla, U. S. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000287 · Cited by 40
Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye
Kim, W., Jang, Y., Yang, J., & Chung, J. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.07.020 · Cited by 36
Phosphoinositide 3-kinase: From viral oncoprotein to drug target
Vogt, P. K., Bader, A. G., & Kang, S. (2005) · Virology · doi:10.1016/j.virol.2005.09.027 · Cited by 40
TSC1-2 tumour suppressor and regulation of mTOR signalling: linking cell growth and proliferation?
Findlay, G. M., Harrington, L. S., & Lamb, R. F. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.11.002 · Cited by 40
TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1
Plescher, M., Teleman, A. A., & Demetriades, C. (2015) · Scientific Reports · doi:10.1038/srep13828 · Cited by 36
Drayer, A. L., Olthof, S. G. M., & Vellenga, E. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0062 · Cited by 41
Gai, Z., Chu, W., Deng, W., Li, W., Li, H. L., He, A., Nellist, M. D., & Wu, G. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw001 · Cited by 41
Sawan, S. A., van Vliet, S., West, D. W. D., Beals, J. W., Paluska, S. A., Burd, N. A., & Moore, D. R. (2018) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00225.2018 · Cited by 40
Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling
Forte, G. M. A., Davie, E., Lie, S., Franz‐Wachtel, M., Ovens, A. J., Wang, T., Oakhill, J. S., Maček, B., Hagan, I., & Petersen, J. (2019) · Journal of Cell Science · doi:10.1242/jcs.223925 · Cited by 39
Nazari, N., Jafari, F., Ghalamfarsa, G., Hadinia, A., Atapour, A., Ahmadi, M., Dolati, S., & Rostamzadeh, D. (2021) · Immunology and Cell Biology · doi:10.1111/imcb.12477 · Cited by 40
Precision Therapy for Epilepsy Related to Brain Malformations
D’Gama, A. M., & Poduri, A. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01122-6 · Cited by 40
Gong, X., Zhang, L., Huang, T., Lin, T. V., Miyares, L. C., Wen, J. H., Hsieh, L. S., & Bordey, A. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv295 · Cited by 39
Kelly, P., Bailey, C. L., Fueger, P. T., Newgard, C. B., Casey, P. J., & Kimple, M. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.069112 · Cited by 39
Gao, Y., & Tian, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411811 · Cited by 39
Rheb signaling and tumorigenesis: mTORC1 and new horizons
Armijo, M. E., Campos, T., Fuentes‐Villalobos, F., Palma, M., Pincheira, R., & Castro, A. F. (2015) · International Journal of Cancer · doi:10.1002/ijc.29707 · Cited by 38
Schöpel, M., Jockers, K. F. G., Düppe, P. M., Autzen, J., Potheraveedu, V. N., Ince, S., Yip, K. T., Heumann, R., Herrmann, C., Scherkenbeck, J., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401291q · Cited by 39
Mammalian target of rapamycin signaling in the podocyte
Inoki, K., & Huber, T. B. (2012) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3283520f38 · Cited by 38
Self-citationA hybrid model for cell proliferation and migration in glioblastoma
Kim, Y., & Roh, S. (2013) · Discrete and Continuous Dynamical Systems - B · doi:10.3934/dcdsb.2013.18.969 · Cited by 39
Xiao, R., Wang, L., Cao, Y., & Zhang, G. (2016) · Ecology and Evolution · doi:10.1002/ece3.2142 · Cited by 38
Sensing the Environment Through Sestrins: Implications for Cellular Metabolism
Parmigiani, A., & Budanov, A. V. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.05.003 · Cited by 40
PEX5 regulates autophagy via the mTORC1-TFEB axis during starvation
Eun, S. Y., Lee, J. N., Nam, I.-K., Liu, Z., So, H., Choe, S., & Park, R. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-017-0007-8 · Cited by 38
Liang, W. S., Vergilio, J., Salhia, B., Huang, H. J., Oki, Y., Garrido‐Laguna, I., Park, H., Westin, J. R., Meric‐Bernstam, F., Fabrizio, D. A., et al. (2018) · The Oncologist · doi:10.1634/theoncologist.2018-0058 · Cited by 38
HCMV modulation of cellular PI3K/AKT/mTOR signaling: New opportunities for therapeutic intervention?
Altman, A. M., Mahmud, J., Nikolovska‐Coleska, Z., & Chan, G. C. T. (2019) · Antiviral Research · doi:10.1016/j.antiviral.2019.01.009 · Cited by 37
Cross-talk between CD38 and TTP Is Essential for Resolution of Inflammation during Microbial Sepsis
Joe, Y., Chen, Y., Park, J., Kim, H. J., Rah, S., Ryu, J., Cho, G. J., Choi, H., Ryter, S. W., Park, J. W., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.090 · Cited by 38
Cai, Y., Xu, G., Wu, F. H., Michelini, F., Chan, C., Qu, X., Selenica, P., Ladewig, E., Castel, P., Cheng, Y., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3232 · Cited by 38
The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization
Lynham, J., & Houry, W. A. (2022) · Biomolecules · doi:10.3390/biom12081045 · Cited by 43
JNK Signaling Promotes Intestinal Tumorigenesis Through Activation of mTOR Complex 1 in ApcΔ716 Mice
Fujishita, T., Aoki, M., & Taketo, M. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.007 · Cited by 38
Zhao, Z., Xu, Q., Wei, R., Wang, W., Ding, D., Yang, Y., Yao, J., Zhang, L., Hu, Y., Wei, G., et al. (2021) · Genome Research · doi:10.1101/gr.271627.120 · Cited by 40
Qin, J., Wang, Z., Hoogeveen-Westerveld, M., Shen, G., Gong, W., Nellist, M., & Xu, W. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.701870 · Cited by 37
An Autoinhibited Noncanonical Mechanism of GTP Hydrolysis by Rheb Maintains mTORC1 Homeostasis
Mazhab-Jafari, M. T., Marshall, C. B., Ishiyama, N., Ho, J., Di Palma, V., Stambolic, V., & Ikura, M. (2012) · Structure · doi:10.1016/j.str.2012.06.013 · Cited by 37
A cellular and molecular basis of leptin resistance
Tan, B., Hedbacker, K., Kelly, L., Zhang, Z., Moura‐Assis, A., Luo, J., Rabinowitz, J. D., & Friedman, J. M. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.01.001 · Cited by 45
Dimova, E. Y., Michiels, C., & Kietzmann, T. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209789649358 · Cited by 37
Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium
Yu, B., Egbejimi, A., Dharmat, R., Xu, P., Zhao, Z., Long, B., Miao, H., Chen, R., Wensel, T. G., Cai, J., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aag3315 · Cited by 38
The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas
Bongaarts, A., van Scheppingen, J., Korotkov, A., Mijnsbergen, C., Anink, J. J., Jansen, F. E., Spliet, W. G. M., den Dunnen, W. F. A., Gruber, V., Scholl, T. O., et al. (2019) · Brain · doi:10.1093/brain/awz370 · Cited by 38
Aberrant expression of TSC2 gene in the newly diagnosed acute leukemia
Xu, Z., Wang, M., Wang, L., Wang, Y., Zhao, X., Rao, Q., & Wang, J. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.01.041 · Cited by 38
Evidence for a molecular link between the tuberous sclerosis complex and the Crumbs complex
Massey‐Harroche, D., Delgrossi, M.-H., Lane, L., Arsanto, J., Borg, J., Billaud, M., & Bivic, A. L. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl485 · Cited by 40
Ribosomal protein S 6 phosphorylation is controlled by TOR and modulated by PKA in C andida albicans
Chowdhury, T., & Köhler, J. R. (2015) · Molecular Microbiology · doi:10.1111/mmi.13130 · Cited by 37
Gu, J., Santiago, L., & Mitchell, B. S. (2004) · Blood · doi:10.1182/blood-2004-10-3864 · Cited by 37
Phosphorylation and binding partner analysis of the TSC1–TSC2 complex
Nellist, M. D., Burgers, P. C., van den Ouweland, A. M. W., Halley, D. J. J., & Luider, T. M. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.05.175 · Cited by 37
Vasudevan, D. M., & Sreekumari, S. (2007) · Jaypee Brothers Medical Publishers (P) Ltd. eBooks · doi:10.5005/jp/books/10897_42 · Cited by 37
Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention
Latosińska, A., Mokou, M., Makridakis, M., Mullen, W., Zoidakis, J., Lygirou, V., Frantzi, M., Katafigiotis, I. S., STRAVODIMOS, K. G., Hupe, M. C., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17279 · Cited by 36
Transcriptional and Epigenetic Regulation by the Mechanistic Target of Rapamycin Complex 1 Pathway
Laribee, R. N. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.10.008 · Cited by 37
Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program
Kikani, C. K., Wu, X., Fogarty, S., Kang, S. A., Dephoure, N., Gygi, S. P., Sabatini, D. M., & Rutter, J. P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804013116 · Cited by 35
Dorsal ruffles enhance activation of Akt by growth factors
Yoshida, S., Pacitto, R., Sesi, C., Kotula, L., & Swanson, J. A. (2018) · Journal of Cell Science · doi:10.1242/jcs.220517 · Cited by 35
Yang, S., Zhang, Y., Ting, C.-Y., Bettedi, L., Kim, K., Ghaniam, E., & Lilly, M. A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.08.006 · Cited by 36
The AMPK/p27Kip1 Pathway as a Novel Target to Promote Autophagy and Resilience in Aged Cells
McKay, L. K., & White, J. P. (2021) · Cells · doi:10.3390/cells10061430 · Cited by 39
mTOR Signaling Components in Tumor Mechanobiology
Gargalionis, A. N., Papavassiliou, K. A., Basdra, E. K., & Papavassiliou, A. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031825 · Cited by 36
Sugiura, H., Yasuda, S., Katsurabayashi, S., Kawano, H., Endo, K., Takasaki, K., Iwasaki, K., Ichikawa, M., Kobayashi, T., Hino, O., et al. (2015) · Nature Communications · doi:10.1038/ncomms7842 · Cited by 37
Metadata
- Authors
- Inoki, K., Li, Y., Xu, T., & Guan, K.-L.
- Affiliations
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-07-17
- Volume
- 17
- Issue
- 15
- Pages
- 1829-1834
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC196227
- OpenAlex
- W2056137479
- Cited by
- 1,911
- References
- 34
- Citations by year
- 2026: 44 · 2025: 68 · 2024: 75 · 2023: 78 · 2022: 72 · 2021: 107 · 2020: 103 · 2019: 73 · 2018: 97 · 2017: 112 · 2016: 111 · 2015: 127 · 2014: 92 · 2013: 101 · 2012: 94
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124709)
- 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 › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- TSC2, GTPase-activating protein, mTOR signaling, tuberous sclerosis complex, S6K phosphorylation, 4E-BP1 phosphorylation, rapamycin, nutrient signaling, cellular energy status, cell growth regulation, Ras family GTPases
- MeSH terms
- Ras Homolog Enriched in Brain Protein, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Antibiotics, Antineoplastic, Cell Division, Cell Line, Dose-Response Relationship, Drug, Genes, Dominant, Guanosine Triphosphate, Humans, Hydrolysis, Models, Biological, Mutation, Neuropeptides, Phosphorylation, Plasmids, Protein Binding, Protein Kinases, Proteins, Repressor Proteins, Time Factors, Protein Biosynthesis, Signal Transduction, Protein Structure, Tertiary, Sirolimus, GTP Phosphohydrolases, Monomeric GTP-Binding Proteins, Tumor Suppressor Proteins, Ribosomal Protein S6 Kinases, 70-kDa, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review