Cited by 249PI3K/AKT/mTOR signaling in cancerT-cell and B-cell ImmunologySignaling Pathways in Disease

The cytotoxic T cell proteome and its shaping by the kinase mTOR

Open access
Hukelmann, Jens L, Anderson, Karen E, Sinclair, Linda V, Grzes, Katarzyna M, Murillo, Alejandro Brenes, Hawkins, Phillip T, Stephens, Len R, Lamond, Angus I +1 more·2016·Nature Immunology

Abstract

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.

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  • Previous studies have revealed poor mRNA-protein correlation in T cells regardless of functional status.

    “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]

    The section “A comparison of the CTL transcriptome and proteome” reports a moderate positive mRNA–protein correlation in cytotoxic T lymphocytes, supporting the claim of imperfect correspondence. It does not establish that this holds for T cells regardless of functional status; the cited analysis is limited to CTLs. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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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
Venue
Nature Immunology
Published
2015-11-09
Volume
17
Issue
1
Pages
104-112
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2191096966
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
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

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