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

Jens L. Hukelmann; Karen E. Anderson; Linda V. Sinclair; Katarzyna M. Grzes; Alejandro Brenes Murillo; Phillip T. Hawkins; Len R. Stephens; Angus I. Lamond; Doreen A. Cantrell

doi:10.1038/ni.3314

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

Jens L. Hukelmann, Karen E. Anderson, Linda V. Sinclair, Katarzyna M. Grzes, Alejandro Brenes Murillo, Phillip T. Hawkins, Len R. Stephens, Angus I. Lamond, Doreen A. Cantrell (Lead / Corresponding author)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

174 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	104-112
Number of pages	9
Journal	Nature Immunology
Volume	17
Issue number	1
Early online date	9 Nov 2015
DOIs	https://doi.org/10.1038/ni.3314
Publication status	Published - Jan 2016

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Author Accepted Manuscript Accepted author manuscript, 681 KBLicence: No Licence / Unknown

How Does O-GlcNAc Transferase Integrate Glucose and Glutamine Metabolism to Control Cytotoxic T Lymphocyte Function?
Cantrell, D. (Investigator)
1/01/16 → 30/06/17
Project: Research
Multidimensional Proteomic Analysis of Metabolic Stress & Cellular Phenotypes (Strategic Grant)
Cantrell, D. (Investigator) & Lamond, A. (Investigator)
1/01/15 → 31/12/19
Project: Research
Serine Kinase Pathways that Determine T Lymphocyte Activation and Cell Fate Choices (Principal Research Fellowship renewal)
Cantrell, D. (Investigator)
1/10/12 → 1/10/24
Project: Research

Cantrell, Doreen
- Cell Signalling and Immunology - Wellcome Trust Principal Research Fellow of Immunology
Person: Academic

Cite this

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title = "The cytotoxic T cell proteome and its shaping by the kinase mTOR",

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.",

author = "Hukelmann, {Jens L.} and Anderson, {Karen E.} and Sinclair, {Linda V.} and Grzes, {Katarzyna M.} and {Brenes Murillo}, Alejandro and Hawkins, {Phillip T.} and Stephens, {Len R.} and Lamond, {Angus I.} and Cantrell, {Doreen A.}",

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doi = "10.1038/ni.3314",

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T1 - The cytotoxic T cell proteome and its shaping by the kinase mTOR

AU - Hukelmann, Jens L.

AU - Anderson, Karen E.

AU - Sinclair, Linda V.

AU - Grzes, Katarzyna M.

AU - Brenes Murillo, Alejandro

AU - Hawkins, Phillip T.

AU - Stephens, Len R.

AU - Lamond, Angus I.

AU - Cantrell, Doreen A.

PY - 2016/1

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N2 - 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.

AB - 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.

U2 - 10.1038/ni.3314

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

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Projects

How Does O-GlcNAc Transferase Integrate Glucose and Glutamine Metabolism to Control Cytotoxic T Lymphocyte Function?

Multidimensional Proteomic Analysis of Metabolic Stress & Cellular Phenotypes (Strategic Grant)

Serine Kinase Pathways that Determine T Lymphocyte Activation and Cell Fate Choices (Principal Research Fellowship renewal)

Profiles

Cantrell, Doreen

Cite this