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

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

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Hukelmann, Jens L, Anderson, Karen E, Sinclair, Linda V, Grzes, Katarzyna M, Murillo, Alejandro Brenes, Hawkins, Phillip T, Stephens, Len R, Lamond, Angus I, Cantrell, Doreen A·2016·Nature Immunology

DOI 10.1038/ni.3314PMC PMC4685757

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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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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: Hukelmann, Jens L
Anderson, Karen E
Sinclair, Linda V
Grzes, Katarzyna M
Hawkins, Phillip T
Stephens, Len R
Lamond, Angus I
Cantrell, Doreen A
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-11-09
Volume: 17
Issue: 1
Pages: 104-112
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.3314
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: green
discovery.dundee.ac.uk
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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The cytotoxic T cell proteome and its shaping by the kinase mTOR

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