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.
authors.affiliation: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee, UK.|Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Jens L
authors.initials: JL
authors.lastname: Hukelmann
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Anderson
authors.affiliation: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee, UK.
authors.forename: Linda V
authors.initials: LV
authors.lastname: Sinclair
authors.affiliation: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee, UK.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Grzes
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Alejandro Brenes
authors.initials: AB
authors.lastname: Murillo
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Hawkins
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: Len R
authors.initials: LR
authors.lastname: Stephens
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
authors.affiliation: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee, UK.
authors.forename: Doreen A
authors.initials: DA
authors.lastname: Cantrell
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002845:Chromatography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D020543:Proteome; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases