Cited by 887PI3K/AKT/mTOR signaling in cancerSignaling Pathways in DiseaseAutophagy in Disease and Therapy

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

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

Open access

Sabers, Candace J., Martin, Mary M., Brunn, Gregory J., Williams, Josie M., Dumont, Francis J., Wiederrecht, Gregory, Abraham, Robert T.·1995·Journal of Biological Chemistry

DOI 10.1074/jbc.270.2.815

Open this paper in CoChat — free account Open PDF

Abstract

The immunosuppressive drug, rapamycin, interferes with an undefined signaling pathway required for the progression of G1-phase T-cells into S phase. Genetic analyses in yeast indicate that binding of rapamycin to its intracellular receptor, FKBP12, generates a toxic complex that inhibits cell growth in G1 phase. These analyses implicated two related proteins, TOR1 and TOR2, as targets of the FKBP12-rapamycin complex in yeast. In this study, we have used a glutathione S-transferase (GST)-FKBP12-rapamycin affinity matrix to isolate putative mammalian targets of rapamycin (mTOR) from tissue extracts. In the presence of rapamycin, immobilized GST-FKBP12 specifically precipitates similar high molecular mass proteins from both rat brain and murine T-lymphoma cell extracts. Binding experiments performed with rapamycin-sensitive and -resistant mutant clones derived from the YAC-1 T-lymphoma cell line demonstrate that the GST-FKBP12-rapamycin complex recovers significantly lower amounts of the candidate mTOR from rapamycin-resistant cell lines. The latter results suggest that mTOR is a relevant target of rapamycin in these cells. Finally, we report the isolation of a full-length mTOR cDNA that encodes a direct ligand for the FKBP12-rapamycin complex. The deduced amino acid sequence of mTOR displays 42 and 45% identity to those of yeast TOR1 and TOR2, respectively. These results strongly suggest that the FKBP12-rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G1- to S-phase progression in T-lymphocytes and other sensitive cell types.

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

Crossref · 10.1074/jbc.270.2.815

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs
Kozak, M. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.20.8125 · Cited by 5,090
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053
Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635
RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509
In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis
Rosenfeld, J., Capdevielle, J., Guillemot, J. C., & Ferrara, P. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90061-b · Cited by 1,239
Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases
Chung, J., Kuo, C. J., Crabtree, G. R., & Blenis, J. (1992) · Cell · doi:10.1016/0092-8674(92)90643-q · Cited by 1,151

Show all 29 references

Research works printed but not linked: 1

Cafferkey, 1993, Mol. Cell. Biol., 13, 6012, 10.1128/MCB.13.10.6012 · DOI

Sorted by citations

Items 201–300 of 885

The immunobiology of mTOR in autoimmunity
Suto, T., & Karonitsch, T. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102373 · Cited by 149
The Complexes of Mammalian Target of Rapamycin
Zhou, H., & Huang, S. (2010) · Current Protein and Peptide Science · doi:10.2174/138920310791824093 · Cited by 153
The Mammalian Target of Rapamycin Regulates C2C12 Myogenesis via a Kinase-independent Mechanism
Erbay, E., & Chen, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100406200 · Cited by 158
Chemical modification of rapamycin: the discovery of SDZ RAD
Sedrani, R. C., Cottens, S., Kallen, J. A., & Schüler, W. (1998) · Transplantation Proceedings · doi:10.1016/s0041-1345(98)00587-9 · Cited by 147
Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression
Woltman, A. M., van der Kooij, S. W., Coffer, P. J., Offringa, R., Daha, M. R., & van Kooten, C. (2003) · Blood · doi:10.1182/blood-2002-06-1688 · Cited by 152
Rapamycin Protects Against High Fat Diet–Induced Obesity in C57BL/6J Mice
Chang, G., Chiu, Y., Wu, Y., Chen, W., Liao, J., Chao, T., & Mao, F. C. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08215fp · Cited by 148
Mammalian Target of Rapamycin: A New Molecular Target for Breast Cancer
Mita, M. M., Mita, A. C., & Rowinsky, E. K. (2003) · Clinical Breast Cancer · doi:10.3816/cbc.2003.n.018 · Cited by 143
Nutrient sensing and metabolic decisions
Lindsley, J. E., & Rutter, J. P. (2004) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpc.2004.06.014 · Cited by 146
The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth ControlPreprint
Hindupur, S. K., González, A., & Hall, M. N. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019141 · Cited by 147
The Role of mTORC1 in Regulating Protein Synthesis and Skeletal Muscle Mass in Response to Various Mechanical Stimuli
Goodman, C. A. (2013) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2013_17 · Cited by 145
mTOR signaling for biological control and cancer
Alayev, A., & Holz, M. K. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24351 · Cited by 143
Protein phosphatase 2A: Who shall regulate the regulator?
Goldberg, Y. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00245-7 · Cited by 139
Mechanisms of resistance to rapamycins
Huang, S., & Houghton, P. J. (2001) · Drug Resistance Updates · doi:10.1054/drup.2002.0227 · Cited by 143
A recollection of mTOR signaling in learning and memoryPreprint
Graber, T. E., McCamphill, P. K., & Sossin, W. S. (2013) · Learning & Memory · doi:10.1101/lm.027664.112 · Cited by 143
Mechanical injury suppresses autophagy regulators and pharmacologic activation of autophagy results in chondroprotection
Caramés, B., Taniguchi, N., Seino, D., Blanco, F. J., DʼLima, D. D., & Lotz, M. (2011) · Arthritis & Rheumatism · doi:10.1002/art.33444 · Cited by 138
Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass
Goodman, C. A. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01011.2018 · Cited by 133
Raptor and mTOR: Subunits of a Nutrient-Sensitive Complex
Kim, D., & Sabatini, D. M. (2004) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-18930-2_15 · Cited by 134
Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt
Asnaghi, L., Calastretti, A., Bevilacqua, A., D’Agnano, I., Gatti, G., Canti, G. L., Delia, D., Capaccioli, S., & Nicolin, A. (2004) · Oncogene · doi:10.1038/sj.onc.1207698 · Cited by 132
Epileptogenesis and Reduced Inward Rectifier Potassium Current in Tuberous Sclerosis Complex‐1–Deficient Astrocytes
Jansen, L. A., Uhlmann, E. J., Crino, P. B., Gutmann, D. H., & Wong, M. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00289.x · Cited by 134
ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells
Fuchs, B. C., Finger, R., Onan, M. C., & Bode, B. P. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00330.2006 · Cited by 137
Mammalian Target of Rapamycin-dependent Phosphorylation of PHAS-I in Four (S/T)P Sites Detected by Phospho-specific Antibodies
Mothe‐Satney, I., Brunn, G. J., McMahon, L. P., Capaldo, C., Abraham, R. T., & Lawrence, J. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006005200 · Cited by 130
Self-citation
Sirolimus Conversion for Patients with Posttransplant Kaposi's Sarcoma
Lebbé, C., Euvrard, S., Barrou, B., Pouteil‐Noble, C., Garnier, J. L., Glotz, D., Legendre, C., & Francèsh, C. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01412.x · Cited by 129
PI3-kinase and TOR: PIKTORing cell growth
Richardson, C. J., Schalm, S. S., & Blenis, J. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2003.12.023 · Cited by 130
Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence
Darici, S., Alkhaldi, H., Horne, G. A., Jørgensen, H. G., Marmiroli, S., & Huang, X. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092934 · Cited by 135
Vertical inhibition of the PI3K/Akt/mTOR pathway for the treatment of osteoarthritis
Chen, J., Crawford, R., & Xiao, Y. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24362 · Cited by 127
How to Choose the Right Inducible Gene Expression System for Mammalian Studies?
Kallunki, T., Barišić, M., Jäättelä, M., & Liu, B. (2019) · Cells · doi:10.3390/cells8080796 · Cited by 140
Predominant Nuclear Localization of Mammalian Target of Rapamycin in Normal and Malignant Cells in Culture
Zhang, X., Shu, L., Hosoi, H., Murti, K. G., & Houghton, P. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202625200 · Cited by 130
Two Motifs in the Translational Repressor PHAS-I Required for Efficient Phosphorylation by Mammalian Target of Rapamycin and for Recognition by Raptor
Choi, K. M., McMahon, L. P., & Lawrence, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301142200 · Cited by 128
Cell Cycle Regulation by the Nutrient-Sensing Mammalian Target of Rapamycin (mTOR) Pathway
Cuyàs, E., Corominas-Faja, B., Joven, J., & Menéndez, J. A. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0888-2_7 · Cited by 128
Renal Cell Carcinoma: New Developments in Molecular Biology and Potential for Targeted Therapies
Costa, L. J., & Drabkin, H. A. (2007) · The Oncologist · doi:10.1634/theoncologist.12-12-1404 · Cited by 126
Role of the mTOR signaling pathway in epilepsy
Meng, X., Yu, J., Song, J., Chi, S., & Tan, L. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.05.029 · Cited by 127
EFFECT OF SIROLIMUS ON THE METABOLISM OF ApoB100- CONTAINING LIPOPROTEINS IN RENAL TRANSPLANT PATIENTS1
Hoogeveen, R. C., Ballantyne, C. M., Pownall, H. J., Opekun, A. R., Hachey, D. L., Jaffe, J. S., Oppermann, S., Kahan, B. D., & Morrisett, J. D. (2001) · Transplantation · doi:10.1097/00007890-200110150-00011 · Cited by 124
Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling
Mousses, S., Wagner, U., Chen, Y., Kim, J. W., Bubendorf, L., Bittner, M. L., Pretlow, T. G., ELKAHLOUN, A. G., Trepel, J. B., & Kallioniemi, O. (2001) · Oncogene · doi:10.1038/sj.onc.1204889 · Cited by 123
Exposure-response relationships and drug interactions of sirolimus
Zimmerman, J. J. (2004) · The AAPS Journal · doi:10.1208/aapsj060428 · Cited by 123
mTOR-Mediated Activation of p70 S6K Induces Differentiation of Pluripotent Human Embryonic Stem Cells
Easley, C. A., Ben‐Yehudah, A., Redinger, C. J., Oliver, S. L., Varum, S., Eisinger, V. M., Carlisle, D. L., Donovan, P. J., & Schatten, G. P. (2010) · Cellular Reprogramming · doi:10.1089/cell.2010.0011 · Cited by 122
Kaposi sarcoma herpesvirus pathogenesis
Mariggiò, G., Koch, S., & Schulz, T. F. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0275 · Cited by 121
Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications
Basheer, A. S., Abas, F., Othman, I., & Naidu, R. (2021) · Cancers · doi:10.3390/cancers13164226 · Cited by 120
A regulatory role for cAMP in phosphatidylinositol 3-kinase/p70 ribosomal S6 kinase-mediated DNA synthesis in platelet-derived-growth-factor-stimulated bovine airway smooth-muscle cells
Scott, P., BELHAM, C. M., Al-Hafidh, J., Chilvers, E. R., Peacock, A. J., Gould, G. W., & Plevin, R. J. (1996) · Biochemical Journal · doi:10.1042/bj3180965 · Cited by 117
Ig Receptor Binding Protein 1 (α4) Is Associated With a Rapamycin-Sensitive Signal Transduction in Lymphocytes Through Direct Binding to the Catalytic Subunit of Protein Phosphatase 2A
Inui, S., Sanjo, H., Maeda, K., Yamamoto, H., Miyamoto, E., & Sakaguchi, N. (1998) · Blood · doi:10.1182/blood.v92.2.539.414k23_539_546 · Cited by 117
A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling
Chen, J., & Fang, Y. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01263-7 · Cited by 119
Drug-Eluting Stents
Woods, T. C., & Marks, A. R. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.55.091902.105243 · Cited by 116
FKBP12‐rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol‐4 kinase activity.
Cardenas, M. E., & Heitman, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00277.x · Cited by 117
A liaison between mTOR signaling, ribosome biogenesis and cancer
Gentilella, A., Kozma, S. C., & Thomas, G. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2015.02.005 · Cited by 120
Functions and regulation of transforming growth factor-beta (TGF-β) in the prostate
Danielpour, D. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2004.12.027 · Cited by 115
Macropinocytosis, mTORC1 and cellular growth control
Yoshida, S., Pacitto, R., Inoki, K., & Swanson, J. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2710-y · Cited by 114
Sanglifehrin−Cyclophilin Interaction: Degradation Work, Synthetic Macrocyclic Analogues, X-ray Crystal Structure, and Binding Data
Sedrani, R. C., Kallen, J., Cabrejas, L. M. M., Papageorgiou, C. D., Senia, F., Rohrbach, S., Wagner, D., Thai, B., Jutzi-Eme, A.-M., France, J., et al. (2003) · Journal of the American Chemical Society · doi:10.1021/ja021327y · Cited by 114
Regulation of Protein Phosphatase 2A Catalytic Activity by alpha4 Protein and Its Yeast Homolog Tap42
Nanahoshi, M., Nishiuma, T., Tsujishita, Y., Hara, K., Inui, S., Sakaguchi, N., & Yonezawa, K. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9493 · Cited by 114
Extracellular Zinc Activates p70 S6 Kinase through the Phosphatidylinositol 3-Kinase Signaling Pathway
Kim, S., Jung, Y.-S., Kim, D., Koh, H., & Chung, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001975200 · Cited by 115
mTOR-Controlled Autophagy Requires Intracellular Ca2+ Signaling
Decuypere, J.-P., Kindt, D., Luyten, T., Welkenhuyzen, K., Missiaen, L., SMEDT, H. D., Bultynck, G., & Parys, J. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061020 · Cited by 113
The mTORC2 signaling network: targets and cross-talks
Ragupathi, A., Kim, C., & Jacinto, E. (2024) · Biochemical Journal · doi:10.1042/bcj20220325 · Cited by 122
The Rapamycin-Binding Domain Governs Substrate Selectivity by the Mammalian Target of Rapamycin
McMahon, L. P., Choi, K. M., Lin, T.-A., Abraham, R. T., & Lawrence, J. C. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7428-7438.2002 · Cited by 113
Self-citation
Activation of Mammalian Target of Rapamycin (mTOR) by Insulin Is Associated with Stimulation of 4EBP1 Binding to Dimeric mTOR Complex 1
Wang, L., Rhodes, C. J., & Lawrence, J. C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603566200 · Cited by 112
Kinome-wide Selectivity Profiling of ATP-competitive Mammalian Target of Rapamycin (mTOR) Inhibitors and Characterization of Their Binding Kinetics
Liu, Q., Kirubakaran, S., Hur, W., Niepel, M., Westover, K. D., Thoreen, C. C., Wang, J., Ni, J., Patricelli, M. P., Vogel, K. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.304485 · Cited by 107
Lifespan-Extending Effects of Royal Jelly and Its Related Substances on the Nematode Caenorhabditis elegans
Honda, Y., Fujita, Y., Maruyama, H., Araki, Y., Ichihara, K., Sato, A., Kojima, T., Tanaka, M., Nozawa, Y., Ito, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023527 · Cited by 109
Cellular and molecular effects of the mTOR inhibitor everolimus
Saran, U., Foti, M., & Dufour, J. (2015) · Clinical Science · doi:10.1042/cs20150149 · Cited by 111
The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer
Gridelli, C., Maione, P., & Rossi, A. (2008) · The Oncologist · doi:10.1634/theoncologist.2007-0171 · Cited by 106
Sanglifehrin A, a Novel Cyclophilin-Binding Compound Showing Immunosuppressive Activity with a New Mechanism of Action
Zenke, G., Strittmatter, U., Fuchs, S., Quesniaux, V. F. J., Brinkmann, V., Schüler, W., Zurini, M. G. M., Enz, A., Billich, A., Sanglier, J., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7165 · Cited by 105
Autophagy and polyglutamine diseases
Jiménez-Sánchez, M., Thomson, F., Zavodszky, E., & Rubinsztein, D. C. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.08.013 · Cited by 105
Antifungal Activities of Antineoplastic Agents: Saccharomyces cerevisiae as a Model System To Study Drug Action
Cardenas, M. E., Cruz, M. C., Poeta, M. D., Chung, N., Perfect, J. R., & Heitman, J. (1999) · Clinical Microbiology Reviews · doi:10.1128/cmr.12.4.583 · Cited by 103
Chemoprevention and Treatment of Experimental Cowden's Disease by mTOR Inhibition with Rapamycin
SQUARIZE, C. H., CASTILHO, R. M., & Gutkind, J. S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0922 · Cited by 103
Autophagy activation is required for influenza A virus-induced apoptosis and replication
Yeganeh, B., Ghavami, S., Rahim, M. N., Klonisch, T. C., Halayko, A. J., & Coombs, K. M. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.10.014 · Cited by 104
Signal-transduction cascades as targets for therapeutic intervention by natural products
Cardenas, M. E., Sanfridson, A., Cutler, N. S., & Heitman, J. (1998) · Trends in Biotechnology · doi:10.1016/s0167-7799(98)01239-6 · Cited by 101
Folate-Conjugated Rapamycin Slows Progression of Polycystic Kidney Disease
Shillingford, J. M., Leamon, C. P., Vlahov, I. R., & Weimbs, T. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012040367 · Cited by 105
Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling
Zhang, C., Wendel, A. A., Keogh, M. R., Harris, T. E., Chen, J., & Coleman, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110730109 · Cited by 102
Control of Translation by the Target of Rapamycin Proteins
Gingras, A., Raught, B., & Sonenberg, N. (2001) · Progress in molecular and subcellular biology · doi:10.1007/978-3-662-09889-9_6 · Cited by 99
Functional interaction between RAFT1/FRAP/mTOR and protein kinase Cδ in the regulation of cap‐dependent initiation of translation
Kumar, V., Pandey, P., Sabatini, D. M., Kumar, M., Majumder, P. K., Bharti, A. K., Carmichael, G., Kufe, D. W., & Kharbanda, S. M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.5.1087 · Cited by 99
Regulation of mTORC1 by Upstream Stimuli
Melick, C. H., & Jewell, J. L. (2020) · Genes · doi:10.3390/genes11090989 · Cited by 104
Emerging role of aging in the progression of NAFLD to HCC
He, Y., Su, Y., Duan, C., Wang, S., He, W. G., Zhang, Y., An, X., & He, M. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101833 · Cited by 100
Dissociation of the eukaryotic initiation factor‐4E/4E‐BP1 complex involves phosphorylation of 4E‐BP1 by an mTOR‐associated kinase
Heesom, K. J., & Denton, R. M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01094-7 · Cited by 99
Insulin-like Growth Factor-I Inhibits Transcriptional Responses of Transforming Growth Factor-β by Phosphatidylinositol 3-Kinase/Akt-dependent Suppression of the Activation of Smad3 but Not Smad2
Song, K. W., Cornelius, S. C., Reiß, M., & Danielpour, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304583200 · Cited by 98
Cholesterol Biosynthesis Supports Myelin Gene Expression and Axon Ensheathment through Modulation of P13K/Akt/mTor Signaling
Mathews, E. S., & Appel, B. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0726-16.2016 · Cited by 97
Glucosamine Activates Autophagy In Vitro and In Vivo
Caramés, B., Kiosses, W. B., Akasaki, Y., Brinson, D. C., Eap, W., Koziol, J. A., & Lotz, M. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37977 · Cited by 96
The mTOR Inhibitor Rapamycin Suppresses DNA Double-Strand Break Repair
Chen, H., Ma, Z., Vanderwaal, R. P., Feng, Z., González-Suárez, I., Wang, S., Zhang, J., Roti, J. L. R., Gonzalo, S., & Zhang, J. (2010) · Radiation Research · doi:10.1667/rr2323.1 · Cited by 96
Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro
Butzal, M., Loges, S., Schweizer, M., Fischer, U., Gehling, U. M., HOSSFELD, D. K., & Fiedler, W. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.07.002 · Cited by 96
4E-binding Proteins, the Suppressors of Eukaryotic Initiation Factor 4E, Are Down-regulated in Cells with Acquired or Intrinsic Resistance to Rapamycin
Dilling, M. B., Germain, G. S., Dudkin, L., Jayaraman, A. L., Zhang, X., Harwood, F. C., & Houghton, P. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110782200 · Cited by 96
T-cell activation through the antigen receptor. Part 2: Role of signaling cascades in T-cell differentiation, anergy, immune senescence, and development of immunotherapy
Nel, A. E., & Slaughter, N. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.124965 · Cited by 96
Focal malformations of cortical development: New vistas for molecular pathogenesis
Lim, K., & Crino, P. B. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.037 · Cited by 98
Ca2+ microdomains in smooth muscle
McCarron, J. G., Chalmers, S., Bradley, K. N., MacMillan, D., & Muir, T. C. (2006) · Cell Calcium · doi:10.1016/j.ceca.2006.08.010 · Cited by 98
Tacrolimus Combined with Two Different Dosagesof Sirolimus in Kidney Transplantation: Results of a Multicenter Study
Vitko, S., Włodarczyk, Z., Kyllönen, L., Czajkowski, Z., Margreiter, R., Bäckman, L., Perner, F., Rigotti, P., Jaques, B. C., Abramowicz, D., et al. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.01193.x · Cited by 94
Differentiating mTOR inhibitors in renal cell carcinoma
Pal, S. K., & Quinn, D. I. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.12.015 · Cited by 96
Deconvoluting mTOR biology
Weber, J. D., & Gutmann, D. H. (2012) · Cell Cycle · doi:10.4161/cc.11.2.19022 · Cited by 97
Frontier of Epilepsy Research - mTOR signaling pathway
Cho, C. (2011) · Experimental & Molecular Medicine · doi:10.3858/emm.2011.43.5.032 · Cited by 93
TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals
Cutler, N. S., Heitman, J., & Cardenas, M. E. (1999) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(99)00121-5 · Cited by 92
Development of everolimus, a novel oral mTOR inhibitor, across a spectrum of diseases
Lebwohl, D., Anak, Ö., Sahmoud, T., Klimovsky, J., Elmroth, I., Haas, T., Posluszny, J. A., Saletan, S., & Berg, W. J. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12122 · Cited by 92
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H., Xiao, X., Pan, Z., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 94
Histone Deacetylase 3 Suppression Increases PH Domain and Leucine-rich Repeat Phosphatase (Phlpp)1 Expression in Chondrocytes to Suppress Akt Signaling and Matrix Secretion
Bradley, E. W., Shull, L. C., & Westendorf, J. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.423723 · Cited by 91
mTOR Signaling in T Cell Immunity and Autoimmunity
Liu, Y., Zhang, D., & Liu, X. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.933957 · Cited by 94
Mammalian target of rapamycin as a therapeutic target in oncology
Abraham, R. T., & Eng, C. H. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.2.209 · Cited by 92
Self-citation
mTOR as a Positive Regulator of Tumor Cell Responses to Hypoxia
Abraham, R. T. (2004) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-18930-2_18 · Cited by 91
Self-citation
mTOR and the differentiation of mesenchymal stem cells
Xiang, X., Zhao, J., Xu, G., Li, Y., & Zhang, W. (2011) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmr041 · Cited by 90
Attenuation of Mammalian Target of Rapamycin Activity by Increased cAMP in 3T3-L1 Adipocytes
Scott, P., & Lawrence, J. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.34496 · Cited by 90
Expansion of the target of rapamycin (TOR) kinase family and function in Leishmania shows that TOR3 is required for acidocalcisome biogenesis and animal infectivity
da Silva, L. M., & Beverley, S. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004599107 · Cited by 88
Cross-talk between IGF-I and TGF-β signaling pathways
Danielpour, D., & SONG, K. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.09.007 · Cited by 91
Rapamycin Prevents Early Onset of Tumorigenesis in an Oral-Specific K- ras and p53 Two-Hit Carcinogenesis Model
Raimondi, A. R., Molinolo, A., & Gutkind, J. S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4645 · Cited by 88
Transcription and Translation Inhibitors in Cancer Treatment
Laham-Karam, N., Pinto, G., Poso, A., & Kokkonen, P. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00276 · Cited by 93
mTOR dysregulation and tuberous sclerosis-related epilepsy
Curatolo, P., Moavero, R., van Scheppingen, J., & Aronica, E. (2018) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1428562 · Cited by 89
Mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitors restore anoikis sensitivity in human breast cancer cell lines with a constitutively activated extracellular-regulated kinase (ERK) pathway.
Fukazawa, H., Noguchi, K., Murakami, Y., & Uehara, Y. (2002) · PubMed · Cited by 85
DEPTOR at the Nexus of Cancer, Metabolism, and Immunity
Caron, A., Briscoe, D. M., Richard, D., & Laplante, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00064.2017 · Cited by 87
Plant target of rapamycin signaling network: Complexes, conservations, and specificities
Liu, Y., & Xiong, Y. (2021) · Journal of Integrative Plant Biology · doi:10.1111/jipb.13212 · Cited by 86
Therapeutic potential of target of rapamycin inhibitors
Easton, J. B., & Houghton, P. J. (2004) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.8.6.551 · Cited by 84

Authors: Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T.
Affiliations: Mayo Clinic (US)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author: Abraham, Robert T.
ORCID: Abraham, Robert T.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1995-01
Volume: 270
Issue: 2
Pages: 815-822
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.270.2.815
OpenAlex: W2158612356
Cited by: 887
References: 29
Citations by year: 2026: 10 · 2025: 20 · 2024: 28 · 2023: 37 · 2022: 38 · 2021: 37 · 2020: 39 · 2019: 31 · 2018: 25 · 2017: 38 · 2016: 25 · 2015: 31 · 2014: 26 · 2013: 31 · 2012: 29
FWCI: 9.91
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9442 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Mayo Foundation for Medical Education and Research
National Institutes of Health
National Institute of General Medical Sciences (R01GM047286, GM47286)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: rapamycin, FKBP12, mTOR, TOR1, TOR2, G1/S transition, T cells, immunosuppressants, rapamycin resistance, YAC-1 cells, cDNA cloning
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, DNA-Binding Proteins, Fungal Proteins, Heat-Shock Proteins, Humans, Molecular Sequence Data, Polyenes, Protein Kinases, Tumor Cells, Cultured, Lymphoma, T-Cell, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Phosphotransferases (Alcohol Group Acceptor), DNA Primers, DNA, Complementary, Cell Cycle Proteins, Phosphatidylinositol 3-Kinases, Sirolimus, Tacrolimus Binding Proteins, Saccharomyces cerevisiae Proteins, Rats, 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

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks