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Licensed Unlicensed Requires Authentication Published by De Gruyter March 10, 2015

Redox regulation of T-cell receptor signaling

  • Luca Simeoni EMAIL logo and Ivan Bogeski
From the journal Biological Chemistry

Abstract

T-cell receptor (TCR) triggering by antigens activates a sophisticated intracellular signaling network leading to transcriptional activation, proliferation and differentiation of T cells. These events ultimately culminate in adaptive immune responses. Over recent years it has become evident that reactive oxygen species (ROS) play an important role in T-cell activation. It is now clear that ROS are involved in the regulation of T-cell mediated physiological and pathological processes. Upon TCR triggering, T cells produce oxidants, which originate from different cellular sources. In addition, within inflamed tissues, T cells are exposed to exocrine ROS produced by activated phagocytes or other ROS-producing cells. Oxidative modifications can have different effects on T-cell function. Indeed, they can stimulate T-cell activation but they can be also detrimental. These opposite effects of oxidation likely depend on different factors such as ROS concentration and source and also on the differentiation status of the T cells. Despite the well-stablished fact that ROS represent important modulators of T-cell activation, the precise molecular mechanisms of their action are far from clear. Here, we summarize the present knowledge on redox regulation of T-cell function with a particular emphasis on the redox regulation of TCR signaling.


Corresponding author: Luca Simeoni, Institute of Molecular and Clinical Immunology, Otto von Guericke University, Leipziger Straße 44, D-39120 Magdeburg, Germany, e-mail:

Acknowledgments

This work was supported by the German Research Foundation (DFG) grants SI861/3-1, SFB854 (project B19), BO3643/3-1, SFB1027 (project C4) and the HOMFOR excellent research grant by the Medical School, University of Saarland.

References

Acuto, O., Di Bartolo, V., and Michel, F. (2008). Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nat. Rev. Immunol. 8, 699–712.10.1038/nri2397Search in Google Scholar PubMed

Akhand, A.A., Du, J., Liu, W., Hossain, K., Miyata, T., Nagase, F., Kato, M., Suzuki, H., and Nakashima, I. (2002). Redox-linked cell surface-oriented signaling for T-cell death. Antioxid. Redox Sign. 4, 445–454.10.1089/15230860260196236Search in Google Scholar PubMed

Albrecht, S.C., Sobotta, M.C., Bausewein, D., Aller, I., Hell, R., Dick, T.P., and Meyer, A.J. (2014). Redesign of genetically encoded biosensors for monitoring mitochondrial redox status in a broad range of model eukaryotes. J. Biomol. Screen. 19, 379–386.10.1177/1087057113499634Search in Google Scholar PubMed

Arndt, B., Poltorak, M., Kowtharapu, B.S., Reichardt, P., Philipsen, L., Lindquist, J.A., Schraven, B., and Simeoni, L. (2013). Analysis of TCR activation kinetics in primary human T cells upon focal or soluble stimulation. J. Immunol. Methods 387, 276–283.10.1016/j.jim.2012.11.006Search in Google Scholar PubMed

Bedard, K. and Krause, K.H. (2007). The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev. 87, 245–313.10.1152/physrev.00044.2005Search in Google Scholar PubMed

Belikov, A.V., Schraven, B., and Simeoni, L. (2014). TCR-triggered extracellular superoxide production is not required for T-cell activation. Cell Commun. Sign. 12, 50.10.1186/s12964-014-0050-1Search in Google Scholar PubMed PubMed Central

Belousov, V.V., Fradkov, A.F., Lukyanov, K.A., Staroverov, D.B., Shakhbazov, K.S., Terskikh, A.V., and Lukyanov, S. (2006). Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat. Methods 3, 281–286.10.1038/nmeth866Search in Google Scholar PubMed

Bogeski, I. and Niemeyer, B.A. (2014). Redox regulation of ion channels. Antioxid. Redox Sign. 21, 859–862.10.1089/ars.2014.6019Search in Google Scholar PubMed PubMed Central

Bogeski, I., Bozem, M., Sternfeld, L., Hofer, H.W., and Schulz, I. (2006). Inhibition of protein tyrosine phosphatase 1B by reactive oxygen species leads to maintenance of Ca2+ influx following store depletion in HEK 293 cells. Cell Calcium 40, 1–10.10.1016/j.ceca.2006.03.003Search in Google Scholar PubMed

Bogeski, I., Kappl, R., Kummerow, C., Gulaboski, R., Hoth, M., and Niemeyer, B.A. (2011). Redox regulation of calcium ion channels: chemical and physiological aspects. Cell Calcium 50, 407–423.10.1016/j.ceca.2011.07.006Search in Google Scholar PubMed

Bogeski, I., Kummerow, C., Al-Ansary, D., Schwarz, E.C., Koehler, R., Kozai, D., Takahashi, N., Peinelt, C., Griesemer, D., Bozem, M., et al. (2010). Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. Sci. Sign. 3, ra24.10.1126/scisignal.2000672Search in Google Scholar

Breckwoldt, M.O., Pfister, F.M., Bradley, P.M., Marinkovic, P., Williams, P.R., Brill, M.S., Plomer, B., Schmalz, A., St Clair, D.K., Naumann, R., et al. (2014). Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Nat. Med. 20, 555–560.10.1038/nm.3520Search in Google Scholar

Burkhardt, J.K., Carrizosa, E., and Shaffer, M.H. (2008). The actin cytoskeleton in T cell activation. Ann. Rev. Immunol. 26, 233–259.10.1146/annurev.immunol.26.021607.090347Search in Google Scholar

Capasso, M., Bhamrah, M.K., Henley, T., Boyd, R.S., Langlais, C., Cain, K., Dinsdale, D., Pulford, K., Khan, M., Musset, B., et al. (2010). HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species. Nat. Immunol. 11, 265–272.10.1038/ni.1843Search in Google Scholar

Caza, T.N., Talaber, G., and Perl, A. (2012). Metabolic regulation of organelle homeostasis in lupus T cells. Clin. Immunol. 144, 200–213.10.1016/j.clim.2012.07.001Search in Google Scholar

Chakraborty, A.K. and Weiss, A. (2014). Insights into the initiation of TCR signaling. Nat. Immunol. 15, 798–807.10.1038/ni.2940Search in Google Scholar

Chakravarti, B. and Abraham, G.N. (2002). Effect of age and oxidative stress on tyrosine phosphorylation of ZAP-70. Mech. Ageing Dev. 123, 297–311.10.1016/S0047-6374(01)00350-5Search in Google Scholar

Chaudhri, G., Clark, I.A., Hunt, N.H., Cowden, W.B., and Ceredig, R. (1986). Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J. Immunol. 137, 2646–2652.10.4049/jimmunol.137.8.2646Search in Google Scholar

Chaudhri, G., Hunt, N.H., Clark, I.A., and Ceredig, R. (1988). Antioxidants inhibit proliferation and cell surface expression of receptors for interleukin-2 and transferrin in T lymphocytes stimulated with phorbol myristate acetate and ionomycin. Cell. Immunol. 115, 204–213.10.1016/0008-8749(88)90174-8Search in Google Scholar

Chiarugi, P. (2008). Src redox regulation: there is more than meets the eye. Mol. Cells 26, 329–337.Search in Google Scholar

Chrobot, A.M., Szaflarska-Szczepanik, A., and Drewa, G. (2000). Antioxidant defense in children with chronic viral hepatitis B and C. Med. Sci. Monit. 6, 713–718.Search in Google Scholar

Ckless, K. (2014). Redox proteomics: from bench to bedside. Adv. Exp. Med. Biol. 806, 301–317.10.1007/978-3-319-06068-2_13Search in Google Scholar PubMed

Corcoran, A. and Cotter, T.G. (2013). Redox regulation of protein kinases. FEBS J. 280, 1944–1965.10.1111/febs.12224Search in Google Scholar PubMed

Crump, K.E., Juneau, D.G., Poole, L.B., Haas, K.M., and Grayson, J.M. (2012). The reversible formation of cysteine sulfenic acid promotes B-cell activation and proliferation. Eur. J. Immunol. 42, 2152–2164.10.1002/eji.201142289Search in Google Scholar PubMed PubMed Central

Cunnick, J.M., Dorsey, J.F., Mei, L., and Wu, J. (1998). Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation. Biochem. Mol. Biol. Int. 45, 887–894.10.1002/iub.7510450506Search in Google Scholar PubMed

Das, J., Ho, M., Zikherman, J., Govern, C., Yang, M., Weiss, A., Chakraborty, A.K., and Roose, J.P. (2009). Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell 136, 337–351.10.1016/j.cell.2008.11.051Search in Google Scholar PubMed PubMed Central

Devadas, S., Zaritskaya, L., Rhee, S.G., Oberley, L., and Williams, M.S. (2002). Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J. Exp. Med. 195, 59–70.10.1084/jem.20010659Search in Google Scholar PubMed PubMed Central

Doherty, E., Oaks, Z., and Perl, A. (2014). Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus. Antioxid. Redox Sign. 21, 56–65.10.1089/ars.2013.5702Search in Google Scholar PubMed PubMed Central

Dornand, J. and Gerber, M. (1989). Inhibition of murine T-cell responses by anti-oxidants: the targets of lipo-oxygenase pathway inhibitors. Immunology 68, 384–391.Search in Google Scholar

D’Oro, U., Sakaguchi, K., Appella, E., and Ashwell, J.D. (1996). Mutational analysis of Lck in CD45-negative T cells: dominant role of tyrosine 394 phosphorylation in kinase activity. Mol. Cell. Biol. 16, 4996–5003.10.1128/MCB.16.9.4996Search in Google Scholar PubMed PubMed Central

Droge, W. (2002). Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47–95.10.1152/physrev.00018.2001Search in Google Scholar PubMed

Ermakova, Y.G., Bilan, D.S., Matlashov, M.E., Mishina, N.M., Markvicheva, K.N., Subach, O.M., Subach, F.V., Bogeski, I., Hoth, M., Enikolopov, G., et al. (2014). Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide. Nat. Commun. 5, 5222.10.1038/ncomms6222Search in Google Scholar PubMed PubMed Central

Feske, S. (2009). ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond. Immunol. Rev. 231, 189–209.10.1111/j.1600-065X.2009.00818.xSearch in Google Scholar PubMed PubMed Central

Feske, S., Gwack, Y., Prakriya, M., Srikanth, S., Puppel, S.H., Tanasa, B., Hogan, P.G., Lewis, R.S., Daly, M., and Rao, A. (2006). A mutation in orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441, 179–185.10.1038/nature04702Search in Google Scholar PubMed

Fidelus, R.K. (1988). The generation of oxygen radicals: a positive signal for lymphocyte activation. Cell. Immunol. 113, 175–182.10.1016/0008-8749(88)90015-9Search in Google Scholar

Fidelus, R.K. and Tsan, M.F. (1986). Enhancement of intracellular glutathione promotes lymphocyte activation by mitogen. Cell. Immunol. 97, 155–163.10.1016/0008-8749(86)90385-0Search in Google Scholar

Fidelus, R.K. and Tsan, M.F. (1987). Glutathione and lymphocyte activation: a function of ageing and auto-immune disease. Immunology 61, 503–508.Search in Google Scholar

Fidelus, R.K., Ginouves, P., Lawrence, D., and Tsan, M.F. (1987). Modulation of intracellular glutathione concentrations alters lymphocyte activation and proliferation. Exp. Cell Res. 170, 269–275.10.1016/0014-4827(87)90305-3Search in Google Scholar

Finkel, T. (1998). Oxygen radicals and signaling. Curr. Opin. Cell Biol. 10, 248–253.10.1016/S0955-0674(98)80147-6Search in Google Scholar

Fratelli, M., Demol, H., Puype, M., Casagrande, S., Eberini, I., Salmona, M., Bonetto, V., Mengozzi, M., Duffieux, F., Miclet, E., et al. (2002). Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc. Natl. Acad. Sci. USA 99, 3505–3510.10.1073/pnas.052592699Search in Google Scholar

Gelderman, K.A., Hultqvist, M., Pizzolla, A., Zhao, M., Nandakumar, K.S., Mattsson, R., and Holmdahl, R. (2007). Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. J. Clin. Invest. 117, 3020–3028.10.1172/JCI31935Search in Google Scholar

Gerber, M., Ball, D., Michel, F., and Crastes de Paulet, A. (1985). Mechanism of enhancing effect of irradiation on production of IL-2. Immunol. Lett. 9, 279–283.10.1016/0165-2478(85)90008-2Search in Google Scholar

Giannoni, E. and Chiarugi, P. (2014). Redox circuitries driving src regulation. Antioxid. Redox Sign. 20, 2011–2025.10.1089/ars.2013.5525Search in Google Scholar

Giannoni, E., Taddei, M.L., and Chiarugi, P. (2010). Src redox regulation: again in the front line. Free Rad. Biol. Med. 49, 516–527.10.1016/j.freeradbiomed.2010.04.025Search in Google Scholar

Gil, L., Martinez, G., Gonzalez, I., Tarinas, A., Alvarez, A., Giuliani, A., Molina, R., Tapanes, R., Perez, J., and Leon, O.S. (2003). Contribution to characterization of oxidative stress in HIV/AIDS patients. Pharmacol. Res. 47, 217–224.10.1016/S1043-6618(02)00320-1Search in Google Scholar

Gilabert, J.A. and Parekh, A.B. (2000). Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current I (CRAC). EMBO J. 19, 6401–6407.10.1093/emboj/19.23.6401Search in Google Scholar

Gill, T. and Levine, A.D. (2013). Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction. J. Biol. Chem. 288, 26246–26255.10.1074/jbc.M113.476895Search in Google Scholar

Glitsch, M.D., Bakowski, D., and Parekh, A.B. (2002). Store-operated Ca2+ entry depends on mitochondrial Ca2+ uptake. EMBO J. 21, 6744–6754.10.1093/emboj/cdf675Search in Google Scholar

Gloire, G., Legrand-Poels, S., and Piette, J. (2006). NF-κB activation by reactive oxygen species: fifteen years later. Biochem. Pharmacol. 72, 1493–1505.10.1016/j.bcp.2006.04.011Search in Google Scholar

Gmunder, H., Roth, S., Eck, H.P., Gallas, H., Mihm, S., and Droge, W. (1990). Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells. Cell. Immunol. 130, 520–528.10.1016/0008-8749(90)90292-YSearch in Google Scholar

Goldsmith, M.A. and Weiss, A. (1987). Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor. Proc. Natl. Acad. Sci. USA 84, 6879–6883.10.1073/pnas.84.19.6879Search in Google Scholar PubMed PubMed Central

Griffith, C.E., Zhang, W., and Wange, R.L. (1998). ZAP-70-dependent and -independent activation of Erk in Jurkat T cells. Differences in signaling induced by H2O2 and CD3 cross-linking. J. Biol. Chem. 273, 10771–10776.10.1074/jbc.273.17.10771Search in Google Scholar PubMed

Gringhuis, S.I., Leow, A., Papendrecht-Van Der Voort, E.A., Remans, P.H., Breedveld, F.C., and Verweij, C.L. (2000). Displacement of linker for activation of T cells from the plasma membrane due to redox balance alterations results in hyporesponsiveness of synovial fluid T lymphocytes in rheumatoid arthritis. J. Immunol. 164, 2170–2179.10.4049/jimmunol.164.4.2170Search in Google Scholar PubMed

Gringhuis, S.I., Papendrecht-van der Voort, E.A., Leow, A., Nivine Levarht, E.W., Breedveld, F.C., and Verweij, C.L. (2002). Effect of redox balance alterations on cellular localization of LAT and downstream T-cell receptor signaling pathways. Mol. Cell. Biol. 22, 400–411.10.1128/MCB.22.2.400-411.2002Search in Google Scholar PubMed PubMed Central

Gutscher, M., Pauleau, A.L., Marty, L., Brach, T., Wabnitz, G.H., Samstag, Y., Meyer, A.J., and Dick, T.P. (2008). Real-time imaging of the intracellular glutathione redox potential. Nat. Methods 5, 553–559.10.1038/nmeth.1212Search in Google Scholar PubMed

Hehner, S.P., Breitkreutz, R., Shubinsky, G., Unsoeld, H., Schulze-Osthoff, K., Schmitz, M.L., and Droge, W. (2000). Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol pool. J. Immunol. 165, 4319–4328.10.4049/jimmunol.165.8.4319Search in Google Scholar

Herzenberg, L.A., De Rosa, S.C., Dubs, J.G., Roederer, M., Anderson, M.T., Ela, S.W., Deresinski, S.C., and Herzenberg, L.A. (1997). Glutathione deficiency is associated with impaired survival in HIV disease. Proc. Natl. Acad. Sci. USA 94, 1967–1972.10.1073/pnas.94.5.1967Search in Google Scholar

Hildeman, D.A., Mitchell, T., Kappler, J., and Marrack, P. (2003). T cell apoptosis and reactive oxygen species. J. Clin. Invest. 111, 575–581.10.1172/JCI200318007Search in Google Scholar

Hildeman, D.A., Mitchell, T., Teague, T.K., Henson, P., Day, B.J., Kappler, J., and Marrack, P.C. (1999). Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 10, 735–744.10.1016/S1074-7613(00)80072-2Search in Google Scholar

Hogan, P.G., Lewis, R.S., and Rao, A. (2010). Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Ann. Rev. Immunol. 28, 491–533.10.1146/annurev.immunol.021908.132550Search in Google Scholar PubMed PubMed Central

Hoth, M. and Penner, R. (1992). Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355, 353–356.10.1038/355353a0Search in Google Scholar PubMed

Hoth, M., Fanger, C.M., and Lewis, R.S. (1997). Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J. Cell Biol. 137, 633–648.10.1083/jcb.137.3.633Search in Google Scholar PubMed PubMed Central

Hoth, M., Button, D.C., and Lewis, R.S. (2000). Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes. Proc. Natl. Acad. Sci. USA 97, 10607–10612.10.1073/pnas.180143997Search in Google Scholar PubMed PubMed Central

Hui, E. and Vale, R.D. (2014). In vitro membrane reconstitution of the T-cell receptor proximal signaling network. Nat. Struct. Mol. Biol. 21, 133–142.10.1038/nsmb.2762Search in Google Scholar PubMed PubMed Central

Hultqvist, M., Olsson, L.M., Gelderman, K.A., and Holmdahl, R. (2009). The protective role of ROS in autoimmune disease. Trends Immunol. 30, 201–208.10.1016/j.it.2009.03.004Search in Google Scholar PubMed

Jackson, S.H., Devadas, S., Kwon, J., Pinto, L.A., and Williams, M.S. (2004). T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat. Immunol. 5, 818–827.10.1038/ni1096Search in Google Scholar PubMed

Jones, R.G., Bui, T., White, C., Madesh, M., Krawczyk, C.M., Lindsten, T., Hawkins, B.J., Kubek, S., Frauwirth, K.A., Wang, Y.L., et al. (2007). The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca2+ homeostasis. Immunity 27, 268–280.10.1016/j.immuni.2007.05.023Search in Google Scholar PubMed PubMed Central

Kabe, Y., Ando, K., Hirao, S., Yoshida, M., and Handa, H. (2005). Redox regulation of NF-κB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid. Redox Sign. 7, 395–403.10.1089/ars.2005.7.395Search in Google Scholar PubMed

Kaminski, M., Kiessling, M., Suss, D., Krammer, P.H., and Gulow, K. (2007). Novel role for mitochondria: protein kinase Ctheta-dependent oxidative signaling organelles in activation-induced T-cell death. Mol. Cell. Biol. 27, 3625–3639.10.1128/MCB.02295-06Search in Google Scholar PubMed PubMed Central

Kaminski, M.M., Sauer, S.W., Klemke, C.D., Suss, D., Okun, J.G., Krammer, P.H., and Gulow, K. (2010). Mitochondrial reactive oxygen species control T cell activation by regulating IL-2 and IL-4 expression: mechanism of ciprofloxacin-mediated immunosuppression. J. Immunol. 184, 4827–4841.10.4049/jimmunol.0901662Search in Google Scholar PubMed

Kaminski, M.M., Roth, D., Sass, S., Sauer, S.W., Krammer, P.H., and Gulow, K. (2012). Manganese superoxide dismutase: a regulator of T cell activation-induced oxidative signaling and cell death. Biochim. Biophys. Acta 1823, 1041–1052.10.1016/j.bbamcr.2012.03.003Search in Google Scholar PubMed

Kaminski, M.M., Roth, D., Krammer, P.H., and Gulow, K. (2013). Mitochondria as oxidative signaling organelles in T-cell activation: physiological role and pathological implications. Arch. Immunol. Ther. Exp. (Warsz.) 61, 367–384.10.1007/s00005-013-0235-0Search in Google Scholar PubMed

Kanner, S.B., Kavanagh, T.J., Grossmann, A., Hu, S.L., Bolen, J.B., Rabinovitch, P.S., and Ledbetter, J.A. (1992). Sulfhydryl oxidation down-regulates T-cell signaling and inhibits tyrosine phosphorylation of phospholipase Cγ 1. Proc. Natl. Acad. Sci. USA 89, 300–304.10.1073/pnas.89.1.300Search in Google Scholar PubMed PubMed Central

Kato, H. and Perl, A. (2014). Mechanistic target of rapamycin complex 1 expands Th17 and IL-4+ CD4-CD8- double-negative T cells and contracts regulatory T cells in systemic lupus erythematosus. J. Immunol. 192, 4134–4144.10.4049/jimmunol.1301859Search in Google Scholar PubMed PubMed Central

Kesarwani, P., Murali, A.K., Al-Khami, A.A., and Mehrotra, S. (2013). Redox regulation of T-cell function: from molecular mechanisms to significance in human health and disease. Antioxid. Redox Sign. 18, 1497–1534.10.1089/ars.2011.4073Search in Google Scholar PubMed PubMed Central

Kettenhofen, N.J. and Wood, M.J. (2010). Formation, reactivity, and detection of protein sulfenic acids. Chem. Res. Toxicol. 23, 1633–1646.10.1021/tx100237wSearch in Google Scholar

Klemke, M., Wabnitz, G.H., Funke, F., Funk, B., Kirchgessner, H., and Samstag, Y. (2008). Oxidation of cofilin mediates T cell hyporesponsiveness under oxidative stress conditions. Immunity 29, 404–413.10.1016/j.immuni.2008.06.016Search in Google Scholar

Kovacic, P. and Jacintho, J.D. (2001). Mechanisms of carcinogenesis: focus on oxidative stress and electron transfer. Curr. Med. Chem. 8, 773–796.10.2174/0929867013373084Search in Google Scholar

Kozai, D., Ogawa, N., and Mori, Y. (2014). Redox regulation of transient receptor potential channels. Antioxid. Redox Sign. 21, 971–986.10.1089/ars.2013.5616Search in Google Scholar

Kummerow, C., Junker, C., Kruse, K., Rieger, H., Quintana, A., and Hoth, M. (2009). The immunological synapse controls local and global calcium signals in T lymphocytes. Immunol. Rev. 231, 132–147.10.1111/j.1600-065X.2009.00811.xSearch in Google Scholar

Kwon, J., Devadas, S., and Williams, M.S. (2003). T cell receptor-stimulated generation of hydrogen peroxide inhibits MEK-ERK activation and lck serine phosphorylation. Free Rad. Biol. Med. 35, 406–417.10.1016/S0891-5849(03)00318-6Search in Google Scholar

Kwon, J., Qu, C.K., Maeng, J.S., Falahati, R., Lee, C., and Williams, M.S. (2005). Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP. EMBO J. 24, 2331–2341.10.1038/sj.emboj.7600706Search in Google Scholar

Kwon, J., Shatynski, K.E., Chen, H., Morand, S., de Deken, X., Miot, F., Leto, T.L., and Williams, M.S. (2010). The non-phagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling. Sci. Sign. 3, ra59.Search in Google Scholar

Lahdenpohja, N. and Hurme, M. (1998). CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells. J. Leukoc. Biol. 63, 775–780.10.1002/jlb.63.6.775Search in Google Scholar

Lee, K. and Esselman, W.J. (2002). Inhibition of PTPs by H2O2 regulates the activation of distinct MAPK pathways. Free Rad. Biol. Med. 33, 1121–1132.10.1016/S0891-5849(02)01000-6Search in Google Scholar

Lee, M., Choy, W.C., and Abid, M.R. (2011). Direct sensing of endothelial oxidants by vascular endothelial growth factor receptor-2 and c-Src. PLoS One 6, e28454.10.1371/journal.pone.0028454Search in Google Scholar PubMed PubMed Central

Leonard, S.E., Reddie, K.G., and Carroll, K.S. (2009). Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. ACS Chem. Biol. 4, 783–799.10.1021/cb900105qSearch in Google Scholar PubMed

Lin, X. and Wang, D. (2004). The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling. Semin. Immunol. 16, 429–435.10.1016/j.smim.2004.08.022Search in Google Scholar PubMed

Lindemann, C. and Leichert, L.I. (2012). Quantitative redox proteomics: the NOxICAT method. Methods Mol. Biol. 893, 387–403.10.1007/978-1-61779-885-6_24Search in Google Scholar PubMed

Liou, J., Kim, M.L., Heo, W.D., Jones, J.T., Myers, J.W., Ferrell, J.E., Jr., and Meyer, T. (2005). STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr. Biol. 15, 1235–1241.10.1016/j.cub.2005.05.055Search in Google Scholar PubMed PubMed Central

Lis, A., Peinelt, C., Beck, A., Parvez, S., Monteilh-Zoller, M., Fleig, A., and Penner, R. (2007). CRACM1, CRACM2, and CRACM3 are store-operated Ca2+ channels with distinct functional properties. Curr. Biol. 17, 794–800.10.1016/j.cub.2007.03.065Search in Google Scholar PubMed PubMed Central

Los, M., Droge, W., Stricker, K., Baeuerle, P.A., and Schulze-Osthoff, K. (1995a). Hydrogen peroxide as a potent activator of T lymphocyte functions. Eur. J. Immunol. 25, 159–165.10.1002/eji.1830250127Search in Google Scholar PubMed

Los, M., Schenk, H., Hexel, K., Baeuerle, P.A., Droge, W., and Schulze-Osthoff, K. (1995b). IL-2 gene expression and NF-κB activation through CD28 requires reactive oxygen production by 5-lipoxygenase. EMBO J. 14, 3731–3740.10.1002/j.1460-2075.1995.tb00043.xSearch in Google Scholar PubMed PubMed Central

Lu, S.P., Lin Feng, M.H., Huang, H.L., Huang, Y.C., Tsou, W.I., and Lai, M.Z. (2007). Reactive oxygen species promote raft formation in T lymphocytes. Free Rad. Biol. Med. 42, 936–944.10.1016/j.freeradbiomed.2006.11.027Search in Google Scholar PubMed

Meyer, A.J. and Dick, T.P. (2010). Fluorescent protein-based redox probes. Antioxid. Redox Sign. 13, 621–650.10.1089/ars.2009.2948Search in Google Scholar PubMed

Michalek, R.D., Nelson, K.J., Holbrook, B.C., Yi, J.S., Stridiron, D., Daniel, L.W., Fetrow, J.S., King, S.B., Poole, L.B., and Grayson, J.M. (2007). The requirement of reversible cysteine sulfenic acid formation for T cell activation and function. J. Immunol. 179, 6456–6467.10.4049/jimmunol.179.10.6456Search in Google Scholar PubMed

Mishina, N.M., Bogeski, I., Bolotin, D.A., Hoth, M., Niemeyer, B.A., Schultz, C., Zagaynova, E.V., Lukyanov, S., and Belousov, V.V. (2012). Can we see PIP3 and hydrogen peroxide with a single probe? Antioxid. Redox Sign. 17, 505–512.Search in Google Scholar

Molina, T.J., Kishihara, K., Siderovski, D.P., van Ewijk, W., Narendran, A., Timms, E., Wakeham, A., Paige, C.J., Hartmann, K.U., Veillette, A., et al. (1992). Profound block in thymocyte development in mice lacking p56lck. Nature 357, 161–164.10.1038/357161a0Search in Google Scholar PubMed

Murphy, M.P. (2009). How mitochondria produce reactive oxygen species. Biochem. J. 417, 1–13.10.1042/BJ20081386Search in Google Scholar PubMed PubMed Central

Murphy, M.P. and Siegel, R.M. (2013). Mitochondrial ROS fire up T cell activation. Immunity 38, 201–202.10.1016/j.immuni.2013.02.005Search in Google Scholar PubMed

Mustelin, T., Vang, T., and Bottini, N. (2005). Protein tyrosine phosphatases and the immune response. Nat. Rev. Immunol. 5, 43–57.10.1038/nri1530Search in Google Scholar PubMed

Nakamura, K., Hori, T., Sato, N., Sugie, K., Kawakami, T., and Yodoi, J. (1993). Redox regulation of a src family protein tyrosine kinase p56lck in T cells. Oncogene 8, 3133–3139.Search in Google Scholar

Negishi, I., Motoyama, N., Nakayama, K., Nakayama, K., Senju, S., Hatakeyama, S., Zhang, Q., Chan, A.C., and Loh, D.Y. (1995). Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376, 435–438.10.1038/376435a0Search in Google Scholar PubMed

Novogrodsky, A., Ravid, A., Rubin, A.L., and Stenzel, K.H. (1982). Hydroxyl radical scavengers inhibit lymphocyte mitogenesis. Proc. Natl. Acad. Sci. USA 79, 1171–1174.10.1073/pnas.79.4.1171Search in Google Scholar PubMed PubMed Central

Nunes, P. and Demaurex, N. (2014). Redox regulation of store-operated Ca2+ entry. Antioxid. Redox Sign. 21, 915–932.10.1089/ars.2013.5615Search in Google Scholar PubMed PubMed Central

Ortona, E., Maselli, A., Delunardo, F., Colasanti, T., Giovannetti, A., and Pierdominici, M. (2014). Relationship between redox status and cell fate in immunity and autoimmunity. Antioxid. Redox Sign. 21, 103–122.10.1089/ars.2013.5752Search in Google Scholar PubMed

O-Uchi, J., Jhun, B.S., Xu, S., Hurst, S., Raffaello, A., Liu, X., Yi, B., Zhang, H., Gross, P., Mishra, J., et al. (2014a). Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2-dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter. Antioxid. Redox Sign. 21, 863–879.10.1089/ars.2013.5394Search in Google Scholar PubMed PubMed Central

O-Uchi, J., Ryu, S.Y., Jhun, B.S., Hurst, S., and Sheu, S.S. (2014b). Mitochondrial ion channels/transporters as sensors and regulators of cellular redox signaling. Antioxid. Redox Sign. 21, 987–1006.10.1089/ars.2013.5681Search in Google Scholar PubMed PubMed Central

Padgett, L.E., Broniowska, K.A., Hansen, P.A., Corbett, J.A., and Tse, H.M. (2013). The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis. Ann. NY Acad. Sci. 1281, 16–35.10.1111/j.1749-6632.2012.06826.xSearch in Google Scholar PubMed PubMed Central

Pani, G., Fischer, K.D., Mlinaric-Rascan, I., and Siminovitch, K.A. (1996). Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase. J. Exp. Med. 184, 839–852.10.1084/jem.184.3.839Search in Google Scholar PubMed PubMed Central

Pani, G., Colavitti, R., Borrello, S., and Galeotti, T. (2000). Endogenous oxygen radicals modulate protein tyrosine phosphorylation and JNK-1 activation in lectin-stimulated thymocytes. Biochem. J. 347, 173–181.10.1042/bj3470173Search in Google Scholar

Parekh, A.B. (2003). Store-operated Ca2+ entry: dynamic interplay between endoplasmic reticulum, mitochondria and plasma membrane. J. Physiol. 547, 333–348.10.1113/jphysiol.2002.034140Search in Google Scholar PubMed PubMed Central

Parekh, A.B. and Putney, J.W., Jr. (2005). Store-operated calcium channels. Physiol. Rev. 85, 757–810.10.1152/physrev.00057.2003Search in Google Scholar PubMed

Patterson, D.A., Rapoport, R., Patterson, M.A., Freed, B.M., and Lempert, N. (1988). Hydrogen peroxide-mediated inhibition of T-cell response to mitogens is a result of direct action on T cells. Arch. Surg. 123, 300–304.10.1001/archsurg.1988.01400270034004Search in Google Scholar PubMed

Paula-Lima, A.C., Adasme, T., and Hidalgo, C. (2014). Contribution of Ca2+ release channels to hippocampal synaptic plasticity and spatial memory: potential redox modulation. Antioxid. Redox Sign. 21, 892–914.10.1089/ars.2013.5796Search in Google Scholar PubMed

Paulsen, C.E., Truong, T.H., Garcia, F.J., Homann, A., Gupta, V., Leonard, S.E., and Carroll, K.S. (2012). Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity. Nat. Chem. Biol. 8, 57–64.10.1038/nchembio.736Search in Google Scholar PubMed PubMed Central

Peralta, D., Bronowska, A.K., Morgan, B., Doka, E., Van Laer, K., Nagy, P., Grater, F., and Dick, T.P. (2015). A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation. Nat. Chem. Biol. 11, 156–163.10.1038/nchembio.1720Search in Google Scholar PubMed

Perl, A. (2013). Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat. Rev. Rheumatol. 9, 674–686.10.1038/nrrheum.2013.147Search in Google Scholar PubMed PubMed Central

Pillay, J., Kamp, V.M., van Hoffen, E., Visser, T., Tak, T., Lammers, J.W., Ulfman, L.H., Leenen, L.P., Pickkers, P., and Koenderman, L. (2012). A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J. Clin. Invest. 122, 327–336.10.1172/JCI57990Search in Google Scholar

Poltorak, M., Meinert, I., Stone, J.C., Schraven, B., and Simeoni, L. (2014). Sos1 regulates sustained TCR-mediated Erk activation. Eur. J. Immunol. 44, 1535–1540.10.1002/eji.201344046Search in Google Scholar

Poole, L.B. (2008). Measurement of protein sulfenic acid content. Current protocols in toxicology/editorial board, Mahin D Maines Chapter 17, Unit17 12.10.1002/0471140856.tx1702s38Search in Google Scholar

Quintana, A. and Hoth, M. (2012). Mitochondrial dynamics and their impact on T cell function. Cell Calc. 52, 57–63.10.1016/j.ceca.2012.02.005Search in Google Scholar

Quintana, A., Pasche, M., Junker, C., Al-Ansary, D., Rieger, H., Kummerow, C., Nunez, L., Villalobos, C., Meraner, P., Becherer, U., et al. (2011). Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. EMBO J. 30, 3895–3912.10.1038/emboj.2011.289Search in Google Scholar

Quintana, A., Schwindling, C., Wenning, A.S., Becherer, U., Rettig, J., Schwarz, E.C., and Hoth, M. (2007). T cell activation requires mitochondrial translocation to the immunological synapse. Proc. Natl. Acad. Sci. USA 104, 14418–14423.10.1073/pnas.0703126104Search in Google Scholar

Rao, A. (1994). NF-ATp: a transcription factor required for the co-ordinate induction of several cytokine genes. Immunol. Today 15, 274–281.10.1016/0167-5699(94)90007-8Search in Google Scholar

Remans, P.H., Gringhuis, S.I., van Laar, J.M., Sanders, M.E., Papendrecht-van der Voort, E.A., Zwartkruis, F.J., Levarht, E.W., Rosas, M., Coffer, P.J., Breedveld, F.C., et al. (2004). Rap1 signaling is required for suppression of Ras-generated reactive oxygen species and protection against oxidative stress in T lymphocytes. J. Immunol. 173, 920–931.10.4049/jimmunol.173.2.920Search in Google Scholar PubMed

Reth, M. (2002). Hydrogen peroxide as second messenger in lymphocyte activation. Nat. Immunol. 3, 1129–1134.10.1038/ni1202-1129Search in Google Scholar PubMed

Reyes, B.M., Danese, S., Sans, M., Fiocchi, C., and Levine, A.D. (2005). Redox equilibrium in mucosal T cells tunes the intestinal TCR signaling threshold. J. Immunol. 175, 2158–2166.10.4049/jimmunol.175.4.2158Search in Google Scholar PubMed

Rolli, V., Gallwitz, M., Wossning, T., Flemming, A., Schamel, W.W., Zurn, C., and Reth, M. (2002). Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol. Cell 10, 1057–1069.10.1016/S1097-2765(02)00739-6Search in Google Scholar

Roose, J. and Weiss, A. (2000). T cells: getting a GRP on Ras. Nat. Immunol. 1, 275–276.10.1038/79713Search in Google Scholar

Roose, J.P., Mollenauer, M., Ho, M., Kurosaki, T., and Weiss, A. (2007). Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. Mol. Cell. Biol. 27, 2732–2745.10.1128/MCB.01882-06Search in Google Scholar

Roth, S. and Droge, W. (1987). Regulation of T-cell activation and T-cell growth factor (TCGF) production by hydrogen peroxide. Cell. Immunol. 108, 417–424.10.1016/0008-8749(87)90224-3Search in Google Scholar

Roth, S. and Droge, W. (1991). Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate. European J. Immunol. 21, 1933–1937.10.1002/eji.1830210823Search in Google Scholar

Sahoo, N., Hoshi, T., and Heinemann, S.H. (2014). Oxidative modulation of voltage-gated potassium channels. Antioxid. Redox Sign. 21, 933–952.10.1089/ars.2013.5614Search in Google Scholar

Samelson, L.E. (2011). Immunoreceptor signaling. Cold Spring Harb. Perspect. Biol. 3, pii: a011510.Search in Google Scholar

Samstag, Y., John, I., and Wabnitz, G.H. (2013). Cofilin: a redox sensitive mediator of actin dynamics during T-cell activation and migration. Immunol. Rev. 256, 30–47.10.1111/imr.12115Search in Google Scholar

Santo-Domingo, J. and Demaurex, N. (2010). Calcium uptake mechanisms of mitochondria. Biochim. Biophys. Acta 1797, 907–912.10.1016/j.bbabio.2010.01.005Search in Google Scholar

Schindl, R., Frischauf, I., Bergsmann, J., Muik, M., Derler, I., Lackner, B., Groschner, K., and Romanin, C. (2009). Plasticity in Ca2+ selectivity of Orai1/Orai3 heteromeric channel. Proc. Natl. Acad. Sci. USA 106, 19623–19628.10.1073/pnas.0907714106Search in Google Scholar

Secrist, J.P., Burns, L.A., Karnitz, L., Koretzky, G.A., and Abraham, R.T. (1993). Stimulatory effects of the protein tyrosine phosphatase inhibitor, pervanadate, on T-cell activation events. J. Biol. Chem. 268, 5886–5893.10.1016/S0021-9258(18)53403-7Search in Google Scholar

Sekkat, C., Dornand, J., and Gerber, M. (1988). Oxidative phenomena are implicated in human T-cell stimulation. Immunology 63, 431–437.Search in Google Scholar

Sena, L.A. and Chandel, N.S. (2012). Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 48, 158–167.10.1016/j.molcel.2012.09.025Search in Google Scholar

Sena, L.A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D.A., Wang, C.R., Schumacker, P.T., Licht, J.D., Perlman, H., et al. (2013). Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 38, 225–236.10.1016/j.immuni.2012.10.020Search in Google Scholar

Seo, Y.H. and Carroll, K.S. (2009). Profiling protein thiol oxidation in tumor cells using sulfenic acid-specific antibodies. Proc. Natl. Acad. Sci. USA 106, 16163–16168.10.1073/pnas.0903015106Search in Google Scholar

Sies, H. (2014). Role of metabolic H2O2 generation: redox signaling and oxidative stress. J. Biol. Chem. 289, 8735–8741.10.1074/jbc.R113.544635Search in Google Scholar

Silic-Benussi, M., Cavallari, I., Vajente, N., Vidali, S., Chieco-Bianchi, L., Di Lisa, F., Saggioro, D., D’Agostino, D.M., and Ciminale, V. (2010). Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary versus transformed cells. Blood 116, 54–62.10.1182/blood-2009-07-235861Search in Google Scholar

Smith-Garvin, J.E., Koretzky, G.A., and Jordan, M.S. (2009). T cell activation. Ann. Rev. Immunol. 27, 591–619.10.1146/annurev.immunol.021908.132706Search in Google Scholar

Smyth, M.J. (1991). Glutathione modulates activation-dependent proliferation of human peripheral blood lymphocyte populations without regulating their activated function. J. Immunol. 146, 1921–1927.10.4049/jimmunol.146.6.1921Search in Google Scholar

Staal, F.J., Ela, S.W., Roederer, M., Anderson, M.T., Herzenberg, L.A., and Herzenberg, L.A. (1992). Glutathione deficiency and human immunodeficiency virus infection. Lancet 339, 909–912.10.1016/0140-6736(92)90939-ZSearch in Google Scholar

Stefanova, I., Saville, M.W., Peters, C., Cleghorn, F.R., Schwartz, D., Venzon, D.J., Weinhold, K.J., Jack, N., Bartholomew, C., Blattner, W.A., et al. (1996). HIV infection-induced posttranslational modification of T cell signaling molecules associated with disease progression. J. Clin. Invest. 98, 1290–1297.10.1172/JCI118915Search in Google Scholar PubMed PubMed Central

Stojilkovic, S.S., Leiva-Salcedo, E., Rokic, M.B., and Coddou, C. (2014). Regulation of ATP-gated P2X channels: from redox signaling to interactions with other proteins. Antioxid. Redox Sign. 21, 953–970.10.1089/ars.2013.5549Search in Google Scholar PubMed PubMed Central

Suthanthiran, M., Anderson, M.E., Sharma, V.K., and Meister, A. (1990). Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. USA 87, 3343–3347.10.1073/pnas.87.9.3343Search in Google Scholar PubMed PubMed Central

Takahashi, N., Kozai, D., Kobayashi, R., Ebert, M., and Mori, Y. (2011). Roles of TRPM2 in oxidative stress. Cell Calcium 50, 279–287.10.1016/j.ceca.2011.04.006Search in Google Scholar

Tatla, S., Woodhead, V., Foreman, J.C., and Chain, B.M. (1999). The role of reactive oxygen species in triggering proliferation and IL-2 secretion in T cells. Free Rad. Biol. Med. 26, 14–24.10.1016/S0891-5849(98)00133-6Search in Google Scholar

Todorovic, S.M. and Jevtovic-Todorovic, V. (2014). Redox regulation of neuronal voltage-gated calcium channels. Antioxid. Redox Sign. 21, 880–891.10.1089/ars.2013.5610Search in Google Scholar

Trevillyan, J.M., Chiou, X.G., Ballaron, S.J., Tang, Q.M., Buko, A., Sheets, M.P., Smith, M.L., Putman, C.B., Wiedeman, P., Tu, N., et al. (1999). Inhibition of p56(lck) tyrosine kinase by isothiazolones. Arch. Biochem. Biophys. 364, 19–29.10.1006/abbi.1999.1099Search in Google Scholar

Tripathi, P. and Hildeman, D. (2004). Sensitization of T cells to apoptosis – a role for ROS? Apoptosis 9, 515–523.10.1023/B:APPT.0000038033.14925.02Search in Google Scholar

Tsui, H.W., Siminovitch, K.A., de Souza, L., and Tsui, F.W. (1993). Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat. Genet. 4, 124–129.10.1038/ng0693-124Search in Google Scholar

Ueda, S., Masutani, H., Nakamura, H., Tanaka, T., Ueno, M., and Yodoi, J. (2002). Redox control of cell death. Antioxid. Redox Sign. 4, 405–414.10.1089/15230860260196209Search in Google Scholar

Unkeless, J.C. and Jin, J. (1997). Inhibitory receptors, ITIM sequences and phosphatases. Curr. Opin. Immunol. 9, 338–343.10.1016/S0952-7915(97)80079-9Search in Google Scholar

Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M., and Telser, J. (2007). Free radicals and antioxidants in normal physiological functions and human disease. J. Biochem. Cell Biol. 39, 44–84.10.1016/j.biocel.2006.07.001Search in Google Scholar

Veillette, A., Dumont, S., and Fournel, M. (1993). Conserved cysteine residues are critical for the enzymatic function of the lymphocyte-specific tyrosine protein kinase p56lck. J. Biol. Chem. 268, 17547–17553.10.1016/S0021-9258(19)85367-XSearch in Google Scholar

Visperas, P.R., Winger, J.A., Horton, T.M., Shah, N.H., Aum, D.J., Tao, A., Barros, T., Yan, Q., Wilson, C.G., Arkin, M.R., et al. (2015). Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 Domains of ZAP-70 and Syk can block phosphopeptide binding. Biochem. J. 465, 149–161.10.1042/BJ20140793Search in Google Scholar PubMed PubMed Central

Wang, H., Kadlecek, T.A., Au-Yeung, B.B., Goodfellow, H.E., Hsu, L.Y., Freedman, T.S., and Weiss, A. (2010). ZAP-70: an essential kinase in T-cell signaling. Cold Spring Harb. Perspect. Biol. 2, a002279.10.1101/cshperspect.a002279Search in Google Scholar PubMed PubMed Central

Wange, R.L. (2000). LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways. Sci. STKE. 2000, re1.10.1126/stke.2000.63.re1Search in Google Scholar PubMed

Warnecke, N., Poltorak, M., Kowtharapu, B.S., Arndt, B., Stone, J.C., Schraven, B., and Simeoni, L. (2012). TCR-mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells. EMBO Rep. 13, 386–391.10.1038/embor.2012.17Search in Google Scholar PubMed PubMed Central

Williams, B.L., Schreiber, K.L., Zhang, W., Wange, R.L., Samelson, L.E., Leibson, P.J., and Abraham, R.T. (1998). Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Mol. Cell. Biol. 18, 1388–1399.10.1128/MCB.18.3.1388Search in Google Scholar PubMed PubMed Central

Williams, M.S. and Kwon, J. (2004). T cell receptor stimulation, reactive oxygen species, and cell signaling. Free Rad. Biol. Med. 37, 1144–1151.10.1016/j.freeradbiomed.2004.05.029Search in Google Scholar PubMed

Yoo, S.K., Starnes, T.W., Deng, Q., and Huttenlocher, A. (2011). Lyn is a redox sensor that mediates leukocyte wound attraction in vivo. Nature 480, 109–112.10.1038/nature10632Search in Google Scholar PubMed PubMed Central

Zhang, S.L., Yu, Y., Roos, J., Kozak, J.A., Deerinck, T.J., Ellisman, M.H., Stauderman, K.A., and Cahalan, M.D. (2005). STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437, 902–905.10.1038/nature04147Search in Google Scholar PubMed PubMed Central

Zorov, D.B., Juhaszova, M., and Sollott, S.J. (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 94, 909–950.10.1152/physrev.00026.2013Search in Google Scholar PubMed PubMed Central

Received: 2014-12-12
Accepted: 2015-2-27
Published Online: 2015-3-10
Published in Print: 2015-5-1

©2015 by De Gruyter

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