The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
The cytotoxic T cell proteome and its shaping by the kinase mTOR
Open accessAbstract
We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for negative control of the production of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) by mTORC1 in CTLs. mTORC1 repressed PtdIns(3,4,5)P3 production and determined the requirement for mTORC2 in activation of the kinase Akt. Our unbiased proteomic analysis thus provides comprehensive understanding of CTL identity and the control of CTL function by mTORC1.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Previous studies have revealed poor mRNA–protein correlation in T cells regardless of functional status23–25”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [23]
Experimental — accuracy not yet measured
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
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
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
Cox, J., Hein, M. Y., Luber, C. A., Paron, I., Nagaraj, N., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.031591 · Cited by 5,180
TM4: a free, open-source system for microarray data management and analysis
Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., Braisted, J., Klapa, M., Currier, T., Thiagarajan, M., et al. (2003) · BioTechniques · doi:10.2144/03342mt01 · Cited by 4,837
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
The Immunological Genome Project: networks of gene expression in immune cells
The Immunological Genome Project Consortium, Heng, T. S. P., Painter, M. W., Elpek, K., Lukacs-Kornek, V., Mauermann, N., Turley, S. J., Koller, D., Kim, F. S., Wagers, A. J., et al. (2008) · Nature Immunology · doi:10.1038/ni1008-1091 · Cited by 1,864
Metabolic Pathways in Immune Cell Activation and Quiescence
Pearce, E. L., & Pearce, E. J. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.005 · Cited by 1,692
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11083 · Cited by 1,477
Palsson-McDermott, E. M., Curtis, A. M., Goel, G., Lauterbach, M. A. R., Sheedy, F. J., Gleeson, L. E., van den Bosch, M. W. M., Quinn, S. R., Domingo-Fernandez, R., Johnston, D. G. W., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.005 · Cited by 1,397
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
Macintyre, A. N., Gerriets, V. A., Nichols, A., Michalek, R. D., Rudolph, M. C., Deoliveira, D., Anderson, S. M., Abel, E. D., Chen, B. J., Hale, L. P., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.004 · Cited by 1,169
Delgoffe, G. M., Pollizzi, K. N., Waickman, A. T., Heikamp, E., Meyers, D. J., Horton, M. R., Xiao, B., Worley, P. F., & Powell, J. D. (2011) · Nature Immunology · doi:10.1038/ni.2005 · Cited by 1,141
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
Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., Lim, D., Peterson, T. R., Choi, Y., Gray, N. S., Yaffe, M. B., et al. (2011) · Science · doi:10.1126/science.1199498 · Cited by 1,084
Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen
Pircher, H., Bürki, K., Lang, R., Hengartner, H., & Zinkernagel, R. M. (1989) · Nature · doi:10.1038/342559a0 · Cited by 1,019
Sinclair, L. V., Rolf, J., Emslie, E., Shi, Y.-B., Taylor, P. M., & Cantrell, D. A. (2013) · Nature Immunology · doi:10.1038/ni.2556 · Cited by 930
Self-citationNakaya, M., Xiao, Y., Zhou, X., Chang, J., Chang, M., Cheng, X., Blonska, M., Lin, X., & Sun, S. (2014) · Immunity · doi:10.1016/j.immuni.2014.04.007 · Cited by 902
Yu, Y., Yoon, S.-O., Poulogiannis, G., Yang, Q., Ma, X. M., Villén, J., Kubica, N., Hoffman, G. R., Cantley, L. C., Gygi, S. P., et al. (2011) · Science · doi:10.1126/science.1199484 · Cited by 864
Jacobs, S. R., Herman, C. E., MacIver, N. J., Wofford, J. A., Wieman, H. L., Hammen, J. J., & Rathmell, J. C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4476 · Cited by 853
Geiger, T., Wehner, A., Schaab, C., Cox, J., & Mann, M. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.014050 · Cited by 797
A “Proteomic Ruler” for Protein Copy Number and Concentration Estimation without Spike-in Standards
Wiśniewski, J. R., Hein, M. Y., Cox, J., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.037309 · Cited by 690
Lucas, C. L., Kuehn, H. S., Zhao, F. R., Niemela, J. E., Deenick, E. K., Palendira, U., Avery, D. T., Moens, L., Cannons, J. L., Biancalana, M., et al. (2013) · Nature Immunology · doi:10.1038/ni.2771 · Cited by 678
Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage
Angulo, I., Vadas, O., Garçon, F., Banham-Hall, E., Plagnol, V., Leahy, T. R., Baxendale, H., Coulter, T. I., Curtis, J. W., Wu, C., et al. (2013) · Science · doi:10.1126/science.1243292 · Cited by 647
Self-citationFinlay, D. K., Rosenzweig, E., Sinclair, L. V., Feijoo-Carnero, C., Hukelmann, J. L., Rolf, J., Panteleyev, A. A., Okkenhaug, K., & Cantrell, D. A. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112607 · Cited by 596
Self-citationKidani, Y., Elsaesser, H., Hock, M. B., Vergnes, L., Williams, K. J., Argus, J. P., Marbois, B. N., Komisopoulou, E., Wilson, E. B., Osborne, T. F., et al. (2013) · Nature Immunology · doi:10.1038/ni.2570 · Cited by 552
Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
García‐Martínez, J. M., Moran, J., Clarke, R. G., Gray, A., Cosulich, S. C., Chresta, C. M., & Alessi, D. R. (2009) · Biochemical Journal · doi:10.1042/bj20090489 · Cited by 473
The facilitative glucose transporter GLUT3: 20 years of distinction
Simpson, I. A., Dwyer, D., Malide, D., Moley, K. H., Travis, A., & Vannucci, S. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90388.2008 · Cited by 473
Multidimensional proteomics for cell biology
Larance, M., & Lamond, A. I. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3970 · Cited by 420
Self-citationmTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Pollizzi, K. N., Patel, C. H., Sun, I., Oh, M. H., Waickman, A. T., Wen, J., Delgoffe, G. M., & Powell, J. D. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77746 · Cited by 417
Interleukin 2 regulates its own receptors.
Smith, K. A., & Cantrell, D. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.3.864 · Cited by 411
Self-citationPhosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
Sinclair, L. V., Finlay, D. K., Feijóo, C. G., Cornish, G. H., Gray, A., Ager, A., Okkenhaug, K., Hagenbeek, T. J., Spits, H., & Cantrell, D. A. (2008) · Nature Immunology · doi:10.1038/ni.1603 · Cited by 400
Self-citationBarnett, S. F., Defeo-Jones, D., Fu, S., Hancock, P. J., Haskell, K., Jones, R. E., Kahana, J. A., Kral, A. M., Leander, K. R., LEE, L. L., et al. (2005) · Biochemical Journal · doi:10.1042/bj20041140 · Cited by 398
The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
Biondi, R. M., Kieloch, A., Currie, R. A., Deak, M., & Alessi, D. R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.16.4380 · Cited by 377
Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation
Best, J. A., Blair, D. A., Knell, J., Yang, E., Mayya, V., Doedens, A. L., Dustin, M. L., & Goldrath, A. W. (2013) · Nature Immunology · doi:10.1038/ni.2536 · Cited by 339
Rao, R. R., Li, Q., Bupp, M. G., & Shrikant, P. A. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.015 · Cited by 305
Quantification of PtdInsP3 molecular species in cells and tissues by mass spectrometry
Clark, J. P., Anderson, K. E., Juvin, V., Smith, T., Karpe, F., Wakelam, M. J. O., Stephens, L., & Hawkins, P. T. (2011) · Nature Methods · doi:10.1038/nmeth.1564 · Cited by 290
Self-citationMacintyre, A. N., Finlay, D. K., Preston, G., Sinclair, L. V., Waugh, C. M., Tamas, P., Feijóo, C. G., Okkenhaug, K., & Cantrell, D. A. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.012 · Cited by 278
Self-citationFeinerman, O., Jentsch, G., Tkach, K. E., Coward, J., Hathorn, M. M., Sneddon, M. W., Emonet, T., Smith, K. A., & Altan-Bonnet, G. Y. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.90 · Cited by 201
Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling
Yang, P., Li, Z., Fu, R., Wu, H., & Li, Z. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.03.020 · Cited by 142
A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells
Ly, T., Ahmad, Y., Shlien, A., Soroka, D. N., Mills, A., Emanuele, M. J., Stratton, M. R., & Lamond, A. I. (2014) · eLife · doi:10.7554/elife.01630 · Cited by 125
Self-citationNavarro, M. N., Goebel, J., Feijoo‐Carnero, C., MORRICE, N. A., & Cantrell, D. A. (2011) · Nature Immunology · doi:10.1038/ni.2008 · Cited by 108
Self-citationWaugh, C. M., Sinclair, L. V., Finlay, D. K., Bayascas, J. R., & Cantrell, D. A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00585-09 · Cited by 77
Self-citationNajafov, A., Shpiro, N., & Alessi, D. R. (2012) · Biochemical Journal · doi:10.1042/bj20121287 · Cited by 66
Cited by
Sorted by citations
Signaling and Function of Interleukin-2 in T Lymphocytes
Ross, S. H., & Cantrell, D. A. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053352 · Cited by 1,025
Self-citationUnraveling the Complex Interplay Between T Cell Metabolism and Function
Geltink, R. I. K., Kyle, R. L., & Pearce, E. L. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053019 · Cited by 849
Redox regulation of immunometabolism
Muri, J., & Köpf, M. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00478-8 · Cited by 519
Metabolic pathways in T cell activation and lineage differentiation
Almeida, L., Lochner, M., Berod, L., & Sparwasser, T. D. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.10.009 · Cited by 492
Myeloid Cell-Derived Arginase in Cancer Immune Response
Grzywa, T. M., Sosnowska, A., Matryba, P., Rydzyńska, Z., Jasiński, M., Nowis, D., & Gołąb, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00938 · Cited by 446
Metadata
- Authors
- Hukelmann, J. L., Anderson, K. E., Sinclair, L. V., Grzes, K. M., Murillo, A. B., Hawkins, P. T., Stephens, L. R., Lamond, A. I., & Cantrell, D. A.
- Affiliations
- University of Dundee (GB)
- Babraham Institute (GB)
- Corresponding author
- Cantrell, Doreen A
- ORCID
- Venue
- Nature Immunology
- Published
- 2015-11-09
- Volume
- 17
- Issue
- 1
- Pages
- 104-112
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4685757
- OpenAlex
- W2191096966
- Semantic Scholar
- f09067c9976f2a9e24edeb52284d6302ec58001a
- Cited by
- 249
- References
- 50
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 31 · 2023: 24 · 2022: 20 · 2021: 29 · 2020: 24 · 2019: 21 · 2018: 27 · 2017: 26 · 2016: 17 · 2015: 1
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (073980, 097418/Z/11/Z, 065975, /Z/11/Z, 105024, 105024/Z/14/Z, 097945/C/11/Z, 097418, 093713/Z/10/A, 073980/Z/03/Z, 093713)
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0415, BBS/E/B/000C0413)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- cytotoxic T lymphocytes, mTORC1, mTORC2, Akt signaling, phosphatidylinositol 3,4,5-trisphosphate, granzymes, metabolic regulation, CD8+ T cell activation, T cell effector function
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cells, Cultured, Chromatography, Enzyme-Linked Immunosorbent Assay, Female, Male, Mass Spectrometry, T-Lymphocytes, Cytotoxic, Immunoblotting, Oligonucleotide Array Sequence Analysis, Proteome, Multiprotein Complexes, Mice, 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
