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

Nature Immunology

Volumn 17, Issue 1, 2016, Pages 104-112

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

^a UNIVERSITY OF DUNDEE   (United Kingdom)

^b BABRAHAM INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 [2 (2,6 DIMETHYLMORPHOLINO) 4 MORPHOLINOPYRIDO[2,3 D]PYRIMIDIN 7 YL] 2 METHOXYBENZENEMETHANOL; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 3; GRANZYME A; GRANZYME B; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PROTEIN KINASE B; PROTEOME; STAT1 PROTEIN; STAT3 PROTEIN; STAT4 PROTEIN; STAT5 PROTEIN; STAT6 PROTEIN; TRANSCRIPTOME; UNCLASSIFIED DRUG; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DEPHOSPHORYLATION; ENZYME ACTIVATION; FEMALE; GLUCOSE TRANSPORT; GLYCOLYSIS; INTRACELLULAR SIGNALING; MALE; MASS SPECTROMETRY; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEOMICS; ANIMAL; CELL CULTURE; CHROMATOGRAPHY; DNA MICROARRAY; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOBLOTTING; IMMUNOLOGY; METABOLISM;

ANIMALS; CELLS, CULTURED; CHROMATOGRAPHY; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; IMMUNOBLOTTING; MALE; MASS SPECTROMETRY; MICE; MULTIPROTEIN COMPLEXES; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEOME; T-LYMPHOCYTES, CYTOTOXIC; TOR SERINE-THREONINE KINASES;

EID: 84951276483     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3314     Document Type: Article

References (49)

1. Heng, T.S.P., & Painter, M.W. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091-1094 (2008
2. Schwanhäusser B., et al. Global quantification of mammalian gene expression control. Nature 473, 337-342 (2011
3. Ly, T., et al A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells. eLife 3 e01630 2014
4. Larance, M., & Lamond, A.I. Multidimensional proteomics for cell biology. Nat. Rev. Mol. Cell Biol. 16, 269-280 (2015
5. Geiger, T., Wehner, A., Schaab, C., Cox, J., & Mann, M. Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Mol. Cell. Proteomics 11, M111.014050 (2012
6. Sinclair L.V., et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat. Immunol. 9, 513-521 (2008
7. Araki K., et al. mTOR regulates memory CD8 T-cell differentiation. Nature 460, 108-112 (2009
8. Pollizzi K.N., et al. mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. J. Clin. Invest. 125, 2090-2108 (2015
9. Hara K., et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273, 14484-14494 (1998
10. Thoreen, C.C., et al A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485 109-113 2012
11. Düvel K., et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39, 171-183 (2010
12. Kidani Y., et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat. Immunol. 14, 489-499 (2013
13. Finlay D.K., et al. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J. Exp. Med. 209, 2441-2453 (2012
14. Yu Y., et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-1326 (2011
15. Hsu P.P., et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-1322 (2011
16. Harrington L.S., et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166, 213-223 (2004
17. Wisńiewski, J.R., Hein, M.Y., Cox, J., & Mann, M.A. proteomic ruler for protein copy number and concentration estimation without spike-in standards. Mol. Cell. Proteomics 13, 3497-3506 (2014
18. Pearce, E.L., & Pearce, E.J. Metabolic pathways in immune cell activation and quiescence. Immunity 38, 633-643 (2013
19. Sinclair L.V., et al. Control of amino-Acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat. Immunol. 14, 500-508 (2013
20. Jacobs S.R., et al. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 180, 4476-4486 (2008
21. Macintyre A.N., et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 20, 61-72 (2014
22. Simpson I.A., et al. The facilitative glucose transporter GLUT3: 20 years of distinction. Am. J. Physiol. Endocrinol. Metab. 295, E242-E253 (2008
23. Smith, K.A., & Cantrell, D.A. Interleukin 2 regulates its own receptors. Proc. Natl. Acad. Sci. USA 82, 864-868 (1985
24. Feinerman O., et al. Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response. Mol. Syst. Biol. 6, 437 (2010
25. Best J.A., et al. Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation. Nat. Immunol. 14, 404-412 (2013
26. García-Martínez J.M., et al. Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem. J. 421, 29-42 (2009
27. Rao, R.R., Li, Q., Bupp, M.R.G., & Shrikant, P.A. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8+ T cell differentiation. Immunity 36, 374-387 (2012
28. Nakaya M., et al. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 40, 692-705 (2014
29. van der Windt G.J.W., et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36, 68-78 (2012
30. Alessi D.R., et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Curr. Biol. 7, 261-269 (1997
31. Barnett S.F., et al. Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem. J. 385, 399-408 (2005
32. Sarbassov, D.D., Guertin, D.A., Ali, S.M., & Sabatini, D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101 (2005
33. Biondi, R.M., Kieloch, A., Currie, R.A., Deak, M., & Alessi, D.R. The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. EMBO J. 20, 4380-4390 (2001
34. Delgoffe G.M., et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12, 295-303 (2011
35. Najafov, A., Shpiro, N., & Alessi, D.R. Akt is efficiently activated by PIF-pocket-And PtdIns(3, 4, 5)P3-dependent mechanisms leading to resistance to PDK1 inhibitors. Biochem. J. 448, 285-295 (2012
36. Waugh, C., Sinclair, L., Finlay, D., Bayascas, J.R., & Cantrell, D. Phosphoinositide (3, 4, 5)-Triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation. Mol. Cell. Biol. 29, 5952-5962 (2009
37. Macintyre A.N., et al. Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity 34, 224-236 (2011
38. Yang, P., Li, Z., Fu, R., Wu, H., & Li, Z. Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling. Cell. Signal. 26, 1853-1862 (2014
39. Palsson-McDermott E.M., et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-Activated macrophages. Cell Metab. 21, 65-80 (2015
40. Angulo I., et al. Phosphoinositide 3-kinase ? gene mutation predisposes to respiratory infection and airway damage. Science 342, 866-871 (2013
41. Lucas C.L., et al. Dominant-Activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110? result in T cell senescence and human immunodeficiency. Nat. Immunol. 15, 88-97 (2014
42. Pircher, H., Bürki, K., Lang, R., Hengartner, H., & Zinkernagel, R.M. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342, 559-561 (1989
43. Wang R., et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35, 871-882 (2011
44. Clark J., et al. Quantification of PtdInsP3 molecular species in cells and tissues by mass spectrometry. Nat. Methods 8, 267-272 (2011
45. Navarro, M.N., Goebel, J., Feijoo-Carnero, C., Morrice, N., & Cantrell, D.A. Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. Nat. Immunol. 12, 352-361 (2011
46. Cox, J., & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367-1372 (2008
47. Cox, J., et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteomics 13, 2513-2526 (2014
48. Da Huang, W., Sherman, B.T., & Lempicki, R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1-13 (2009
49. Saeed, A.I., et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34, 374-378 (2003