Functional significance of zinc-related signaling pathways in immune cells

Annual Review of Nutrition

Volumn 29, Issue , 2009, Pages 133-152

  Haase, Hajo ^a   Rink, Lothar ^a  

^a RWTH AACHEN UNIVERSITY   (Germany)

Author keywords

Signal transduction; Zinc homeostasis; Zinc transporter

Indexed keywords

CASPASE; CYTOKINE; METALLOTHIONEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE PHOSPHATASE; NITRIC OXIDE SYNTHASE; PROTEIN; PROTEIN MTF 1; PROTEIN TRAF 6; PROTEIN TYROSINE PHOSPHATASE; TRACE ELEMENT; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; ZINC; ZINC ION; ZINC TRANSPORTER;

ADAPTIVE IMMUNITY; B LYMPHOCYTE; CELL ACTIVITY; CELL FUNCTION; CYTOKINE PRODUCTION; DENDRITIC CELL; GRANULOCYTE; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; IMMUNITY; IMMUNOCOMPETENT CELL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INNATE IMMUNITY; MACROPHAGE; MAST CELL; MOLECULAR BIOLOGY; MONOCYTE; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; ZINC DEFICIENCY;

APOPTOSIS; HUMANS; IMMUNITY; INFECTION; SIGNAL TRANSDUCTION; ZINC;

EID: 59849093433     PISSN: 01999885     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-nutr-080508-141119     Document Type: Review

References (144)

1. An WL, Bjorkdahl C, Liu R, Cowburn RF,Winblad B, Pei JJ. 2005. Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells. J. Neurochem. 92:1104-15
2. Andreini C, Banci L, Bertini I, Rosato A. 2006. Counting the zinc-proteins encoded in the human genome. J. Proteome Res. 5:196-201
3. Auld DS. 2001. Zinc coordination sphere in biochemical zinc sites. Biometals 14:271-313
4. Aydemir TB, Blanchard RK, Cousins RJ. 2006. Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations. Proc. Natl. Acad. Sci. USA 103:1699-704
5. Barford D, Das AK, Egloff MP. 1998. The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu. Rev. Biophys. Biomol. Struct. 27:133-64
6. Beach RS, Gershwin ME,Hurley LS. 1982. Gestational zinc deprivation in mice: persistence of immunodeficiency for three generations. Science 218:469-71
7. Beck FW, Li Y, Bao B, Prasad AS, Sarkar FH. 2006. Evidence for reprogramming global gene expression during zinc deficiency in the HUT-78 cell line. Nutrition 22:1045-56
8. Begum NA, Kobayashi M, Moriwaki Y, Matsumoto M, Toyoshima K, Seya T. 2002. Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures. Genomics 80:630-45
9. Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, et al. 2004. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat. Immunol. 5:1052-60
10. Brautigan DL, Bornstein P, Gallis B. 1981. Phosphotyrosyl-protein phosphatase. Specific inhibition by Zn. J. Biol. Chem. 256:6519-22
11. Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K. 2002. Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev. Cell 2:567-78
12. Buxaderas SC, Farre-Rovira R. 1985. Whole blood and serum zinc levels in relation to sex and age. Rev. Esp. Fisiol. 41:463-70
13. Cakman I, Rohwer J, Schutz RM, Kirchner H, Rink L. 1996. Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mech. Ageing Dev. 87:197-209
14. Cantuaria AA. 1977. Sperm immobilizing antibodies in the serum and cervicovaginal secretions of infertile and normal women. Br. J. Obstet. Gynaecol. 84:865-68
15. Cho YH, Lee SJ, Lee JY, Kim SW, Lee CB, et al. 2002. Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis. Int. J. Antimicrob. Agents 19:576-82
16. Chow LM, Fournel M, Davidson D, Veillette A. 1993. Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk. Nature 365:156-60
17. Colucci F, Di Santo JP, Leibson PJ. 2002. Natural killer cell activation in mice and men: different triggers for similar weapons? Nat. Immunol. 3:807-13
18. Conti M, Beavo J. 2007. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu. Rev. Biochem. 76:481-511
19. Cook-Mills JM, Fraker PJ. 1993. Functional capacity of the residual lymphocytes from zinc-deficient adult mice. Br. J. Nutr. 69:835-48
20. Cousins RJ, Blanchard RK, Popp MP, Liu L, Cao J, et al. 2003. A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells. Proc. Natl. Acad. Sci. USA 100:6952-57
21. Cousins RJ, Leinart AS. 1988. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 2:2884-90
22. Cousins RJ, Liuzzi JP, Lichten LA. 2006. Mammalian zinc transport, trafficking, and signals. J. Biol. Chem. 281:24085-89
23. Coyle P, Philcox JC, Rofe AM. 1995. Metallothionein induction in cultured rat hepatocytes by arthritic rat serum, activated macrophages, interleukin-6, interleukin-11 and leukaemia inhibitory factor. Inflamm. Res. 44:475-81
24. Csermely P, Gueth S, Somogyi J. 1987. The tumor promoter tetradecanoyl-phorbol-acetate (TPA) elicits the redistribution of zinc in subcellular fractions of rabbit thymocytes measured by X-ray fluorescence. Biochem. Biophys. Res. Commun. 144:863-68
25. Csermely P, Somogyi J. 1989. Zinc as a possible mediator of signal transduction in T lymphocytes. Acta Physiol. Hung. 74:195-99
26. Csermely P, Szamel M, Resch K, Somogyi J. 1988. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes. J. Biol. Chem. 263:6487-90
27. Csermely P, Szamel M, Resch K, Somogyi J. 1988. Zinc increases the affinity of phorbol ester receptor in T lymphocytes. Biochem. Biophys. Res. Commun. 154:578-83
28. Deng L, Wang C, Spencer E, Yang L, Braun A, et al. 2000. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103:351-61
29. Donnelly TE Jr. 1978. Effects of zinc chloride on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. Biochim. Biophys. Acta 522:151-60
30. Duke RC, Chervenak R, Cohen JJ. 1983. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc. Natl. Acad. Sci. USA 80:6361-65
31. Eom SJ, Kim EY, Lee JE, Kang HJ, Shim J, et al. 2001. Zn(2+) induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase. Mol. Pharmacol. 59:981-86
32. Erie JC, Good JA, Butz JA, Pulido JS. 2008. Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration. Am. J. Ophthalmol. 147:276-82
33. Faber C, Gabriel P, Ibs KH, Rink L. 2004. Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response. Bone Marrow Transplant. 33:1241-46
34. Fernandes G, Nair M, Onoe K, Tanaka T, Floyd R, Good RA. 1979. Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice. Proc. Natl. Acad. Sci. USA 76:457-61
35. Forbes IJ, Zalewski PD, Giannakis C, Petkoff HS, Cowled PA. 1990. Interaction between protein kinase C and regulatory ligand is enhanced by a chelatable pool of cellular zinc. Biochim. Biophys. Acta 1053:113-17
36. Fraker PJ, King LE. 2004. Reprogramming of the immune system during zinc deficiency. Annu. Rev. Nutr. 24:277-98
37. Francis SH, Colbran JL, McAllister-Lucas LM, Corbin JD. 1994. Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase. J. Biol. Chem. 269:22477-80
38. Gao X, Du Z, Patel TB. 2005. Copper and zinc inhibit Galphas function: a nucleotide-free state of Galphas induced by Cu2+ and Zn2+. J. Biol. Chem. 280:2579-86
39. Glesne D, Vogt S, Maser J, Legnini D, Huberman E. 2006. Regulatory properties and cellular redistribution of zinc during macrophage differentiation of human leukemia cells. J. Struct. Biol. 155:2-11
40. Gomez Y, Arocha F, Espinoza F, Fernandez D, Vasquez A, Granadillo V. 2007. Zinc levels in prostatic fluid of patients with prostate pathologies. Invest. Clin. 48:287-94
41. Gustafson GT. 1967. Heavy metals in rat mast cell granules. Lab Invest. 17:588-98
42. Haase H, Maret W. 2003. Intracellular zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling. Exp. Cell Res. 291:289-98
43. Haase H, Maret W. 2004. A differential assay for the reduced and oxidized states of metallothionein and thionein. Anal. Biochem. 333:19-26
44. Haase H, Maret W. 2005. Fluctuations of cellular, available zinc modulate insulin signaling via inhibition of protein tyrosine phosphatases. J. Trace Elem. Med. Biol. 19:37-42
45. Haase H, MaretW.2008. Partial oxidation and oxidative polymerization of metallothionein. Electrophoresis 29:4169-76
46. Haase H, Mazzatti DJ, White A, Ibs KH, Engelhardt G, et al. 2007. Differential gene expression after zinc supplementation and deprivation in human leukocyte subsets. Mol. Med. 13:362-70
47. Haase H, Mocchegiani E, Rink L. 2006. Correlation between zinc status and immune function in the elderly. Biogerontology 7:421-28
48. Haase H, Ober-Blobaum JL, Engelhardt G, Hebel S, Heit A, et al. 2008. Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes. J. Immunol. 181:6491-502
49. Hansson A. 1996. Extracellular zinc ions induces mitogen-activated protein kinase activity and protein tyrosine phosphorylation in bombesin-sensitive Swiss 3T3 fibroblasts. Arch. Biochem. Biophys. 328:233-38
50. Heuchel R, Radtke F, Georgiev O, Stark G, Aguet M, Schaffner W. 1994. The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. EMBO J. 13:2870-75
51. Ho LH, Ruffin RE, Murgia C, Li L, Krilis SA, Zalewski PD. 2004. Labile zinc and zinc transporter ZnT4 in mast cell granules: role in regulation of caspase activation and NF-kappaB translocation. J. Immunol. 172:7750-60
52. Ho Y, Samarasinghe R, Knoch ME, Lewis M, Aizenman E, Defranco DB. 2008. Selective inhibition of MAPK phosphatases by zinc accounts for ERK1/2-dependent oxidative neuronal cell death. Mol. Pharmacol. 74:1141-51
53. Huang J, Zhang D, Xing W, Ma X, Yin Y, et al. 2008. An approach to assay calcineurin activity and the inhibitory effect of zinc ion. Anal. Biochem. 375:385-87
54. Hubbard SR, Bishop WR, Kirschmeier P, George SJ, Cramer SP, Hendrickson WA. 1991. Identification and characterization of zinc binding sites in protein kinase C. Science 254:1776-79
55. Huse M, Eck MJ, Harrison SC. 1998. A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J. Biol. Chem. 273:18729-33
56. Ibs KH, Rink L. 2003. Zinc-altered immune function. J. Nutr. 133:1452-56S
57. Jackson MJ. 1989. Physiology of zinc: general aspects. In Zinc in Human Biology, ed. CF Mills, pp. 1-14. London: Springer-Verlag
58. Jirakulaporn T, Muslin AJ. 2004. Cation diffusion facilitator proteins modulate Raf-1 activity. J. Biol. Chem. 279:27807-15
59. Kabu K, Yamasaki S, Kamimura D, Ito Y, Hasegawa A, et al. 2006. Zinc is required for Fc epsilon RI-mediated mast cell activation. J. Immunol. 177:1296-305
60. Kahmann L, Uciechowski P, Warmuth S, Plumakers B, Gressner AM, et al. 2008. Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res. 11:227-37
61. Kawagoe T, Sato S, Jung A, Yamamoto M, Matsui K, et al. 2007. Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling. J. Exp. Med. 204:1013-24
62. Kay AR, Toth K. 2008. Is zinc a neuromodulator? Sci. Signal. 1:re3
63. Keen CL, Gershwin ME. 1990. Zinc deficiency and immune function. Annu. Rev. Nutr. 10:415-31
64. Kim PW, Sun ZY, Blacklow SC,Wagner G, Eck MJ. 2003. A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science 301:1725-28
65. Kim S, Jung Y, Kim D, Koh H, Chung J. 2000. Extracellular zinc activates p70 S6 kinase through the phosphatidylinositol 3-kinase signaling pathway. J. Biol. Chem. 275:25979-84
66. 2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 290:L1028-35
67. Kitamura H, Morikawa H, Kamon H, Iguchi M, Hojyo S, et al. 2006. Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat. Immunol. 7:971-77
68. Klein C, Heyduk T, Sunahara RK. 2004. Zinc inhibition of adenylyl cyclase correlates with conformational changes in the enzyme. Cell Signal. 16:1177-85
69. Klein C, Sunahara RK, Hudson TY, Heyduk T, Howlett AC. 2002. Zinc inhibition of cAMP signaling. J. Biol. Chem. 277:11859-65
70. Knapp LT, Klann E. 2000. Superoxide-induced stimulation of protein kinase C via thiol modification and modulation of zinc content. J. Biol. Chem. 275:24136-45
71. Kojima C, Kawakami A, Takei T, Nitta K, Yoshida M. 2007. Angiotensin-converting enzyme inhibitor attenuates monocyte adhesion to vascular endothelium through modulation of intracellular zinc. J. Pharmacol. Exp. Ther. 323:855-60
72. Korichneva I, Hoyos B, Chua R, Levi E, Hammerling U. 2002. Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen. J. Biol. Chem. 277:44327-31
73. Krezel A, Maret W. 2007. Dual nanomolar and picomolar Zn(II) binding properties of metallothionein. J. Am. Chem. Soc. 129:10911-21
74. Kroncke KD, Fehsel K, Schmidt T, Zenke FT, Dasting I, et al. 1994. Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9. Biochem. Biophys. Res. Commun. 200:1105-10
75. Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, et al. 2002. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat. Genet. 31:239-40
76. Laity JH, Andrews GK. 2007. Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1). Arch. Biochem. Biophys. 463:201-10
77. Lamothe B, Campos AD,Webster WK, Gopinathan A, Hur L, Darnay BG. 2008. The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL. J. Biol. Chem. 283:24871-80
78. Langmade SJ, Ravindra R, Daniels PJ, Andrews GK. 2000. The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J. Biol. Chem. 275:34803-9
79. LaRochelle O, Gagne V, Charron J, Soh JW, Seguin C. 2001. Phosphorylation is involved in the activation of metal-regulatory transcription factor 1 in response to metal ions. J. Biol. Chem. 276:41879-88
80. Leibbrandt ME, Khokha R, Koropatnick J. 1994. Antisense down-regulation of metallothionein in a human monocytic cell line alters adherence, invasion, and the respiratory burst. Cell Growth Differ. 5:17-25
81. Leibbrandt ME, Koropatnick J. 1994. Activation of human monocytes with lipopolysaccharide induces metallothionein expression and is diminished by zinc. Toxicol. Appl. Pharmacol. 124:72-81
82. Lepage LM, Giesbrecht JA, Taylor CG. 1999. Expression of T lymphocyte p56(lck), a zinc-finger signal transduction protein, is elevated by dietary zinc deficiency and diet restriction in mice. J. Nutr. 129:620-27
83. Lin RS, Rodriguez C, Veillette A, Lodish HF. 1998. Zinc is essential for binding of p56(lck) to CD4 and CD8alpha. J. Biol. Chem. 273:32878-82
84. Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, et al. 2005. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc. Natl. Acad. Sci. USA 102:6843-48
85. Macian F. 2005. NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5:472-84
86. Maret W. 2000. The function of zinc metallothionein: a link between cellular zinc and redox state. J. Nutr. 130:1455-58S
87. Maret W. 2006. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid. Redox Signal. 8:1419-41
88. Maret W, Jacob C, Vallee BL, Fischer EH. 1999. Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc. Natl. Acad. Sci. USA 96:1936-40
89. Metz CH, Schroder AK, Overbeck S, Kahmann L, Plumakers B, Rink L. 2007. T-helper type 1 cytokine release is enhanced by in vitro zinc supplementation due to increased natural killer cells. Nutrition 23:157-63
90. Moore JB, Blanchard RK, McCormack WT, Cousins RJ. 2001. cDNA array analysis identifies thymic LCK as upregulated in moderate murine zinc deficiency before T-lymphocyte population changes. J. Nutr. 131:3189-96
91. Mustelin T, Tasken K. 2003. Positive and negative regulation of T-cell activation through kinases and phosphatases. Biochem. J. 371:15-27
92. Muzzioli M, Stecconi R, Donnini A, Re F, Provinciali M. 2007. Zinc improves the development of human CD34+ cell progenitors towards natural killer cells and induces the expression of GATA-3 transcription factor. Int. J. Biochem. Cell Biol. 39:955-65
93. Newsome DA. 2008. A randomized, prospective, placebo-controlled clinical trial of a novel zinc-monocysteine compound in age-related macular degeneration. Curr. Eye Res. 33:591-98
94. Opipari AWJr, Boguski MS, Dixit VM. 1990. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J. Biol. Chem. 265:14705-8
95. Overbeck S, Uciechowski P, Ackland ML, Ford D, Rink L. 2008. Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9. J. Leukoc. Biol. 83:368-80
96. Palacios EH, Weiss A. 2004. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene 23:7990-8000
97. Pallen CJ,Wang JH. 1986. Stoichiometry and dynamic interaction of metal ion activators with calcineurin phosphatase. J. Biol. Chem. 261:16115-20
98. Park JA, Koh JY. 1999. Induction of an immediate early gene egr-1 by zinc through extracellular signal-regulated kinase activation in cortical culture: its role in zinc-induced neuronal death. J. Neurochem. 73:450-56
99. Percival MD, Yeh B, Falgueyret JP. 1997. Zinc dependent activation of cAMP-specific phosphodiesterase (PDE4A). Biochem. Biophys. Res. Commun. 241:175-80
100. Pernelle JJ, Creuzet C, Loeb J, Gacon G. 1991. Phosphorylation of the lymphoid cell kinase p56lck is stimulated by micromolar concentrations of Zn2+. FEBS Lett. 281:278-82
101. Philcox JC, Coyle P, Michalska A, Choo KH, Rofe AM. 1995. Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression. Biochem. J. 308:543-46
102. Prasad AS. 2000. Effects of zinc deficiency on immune functions. J. Trace Elem. Exp. Med. 13:1-20
103. Prasad AS. 2007. Zinc: mechanisms of host defense. J. Nutr. 137:1345-49
104. Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH. 2004. Antioxidant effect of zinc in humans. Free Radic. Biol. Med. 37:1182-90
105. Prasad AS, Miale A Jr, Farid Z, Sandstead HH, Schulert AR. 1963. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypogonadism. J. Lab. Clin. Med. 61:537-49
106. Radtke F, Heuchel R, Georgiev O, Hergersberg M, Gariglio M, et al. 1993. Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter. EMBO J. 12:1355-62
107. Riccioli A, Starace D, Galli R, Fuso A, Scarpa S, et al. 2006. Sertoli cells initiate testicular innate immune responses through TLR activation. J. Immunol. 177:7122-30
108. Rink L, Gabriel P. 2001. Extracellular and immunological actions of zinc. Biometals 14:367-83
109. Rink L, Haase H. 2007. Zinc homeostasis and immunity. Trends Immunol. 28:1-4
110. Romir J, Lilie H, Egerer-Sieber C, Bauer F, Sticht H, Muller YA. 2007. Crystal structure analysis and solution studies of human Lck-SH3; zinc-induced homodimerization competes with the binding of proline-rich motifs. J. Mol. Biol. 365:1417-28
111. Saito H. 1990. Innervation of the guinea pig spleen studied by electron microscopy. Am. J. Anat. 189:213-35
112. Saydam N, Adams TK, Steiner F, Schaffner W, Freedman JH. 2002. Regulation of metallothionein transcription by the metal-responsive transcription factor MTF-1: identification of signal transduction cascades that control metal-inducible transcription. J. Biol. Chem. 277:20438-45
113. Schroeder JJ, Cousins RJ. 1990. Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Proc. Natl. Acad. Sci. USA 87:3137-41
114. Spahl DU, Berendji-Grun D, Suschek CV, Kolb-Bachofen V, Kroncke KD. 2003. Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release. Proc. Natl. Acad. Sci. USA 100:13952-57
115. Srivastava A, Chowdhury AR, Setty BS. 1986. Testicular regulation and sub-cellular distribution of zinc in the epididymis and vas deferens of rhesus monkey (Macaca mulatta). Acta Endocrinol. (Copenh.) 113:440-49
116. Stennicke HR, Salvesen GS. 1997. Biochemical characteristics of caspases-3, -6, -7, and -8. J. Biol. Chem. 272:25719-23
117. Stitt MS, Wasserloos KJ, Tang X, Liu X, Pitt BR, St Croix CM. 2006. Nitric oxide-induced nuclear translocation of the metal responsive transcription factor, MTF-1 is mediated by zinc release from metallothionein. Vascul. Pharmacol. 44:149-55
118. Sugiura T, Kuroda E, Yamashita U. 2004. Dysfunction of macrophages in metallothionein-knock out mice. J. UOEH 26:193-205
119. Sun G, Budde RJ. 1999. Substitution studies of the second divalent metal cation requirement of protein tyrosine kinase CSK. Biochemistry 38:5659-65
120. Suzuki N, Suzuki S, Millar DG, Unno M, Hara H, et al. 2006. A critical role for the innate immune signaling molecule IRAK-4 in T cell activation. Science 311:1927-32
121. Takahashi K, Akaishi E, Abe Y, Ishikawa R, Tanaka S, et al. 2003. Zinc inhibits calcineurin activity in vitro by competing with nickel. Biochem. Biophys. Res. Commun. 307:64-68
122. Tan SL, Parker PJ. 2003. Emerging and diverse roles of protein kinase C in immune cell signalling. Biochem. J. 376:545-52
123. Tanaka S, Akaishi E, Hosaka K, Okamura S, Kubohara Y. 2005. Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells. Biochem. Biophys. Res. Commun. 335:162-67
124. Tang X, Shay NF. 2001. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J. Nutr. 131:1414-20
125. Taylor KM,Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson RI. 2008. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology 149:4912-20
126. Thornbury KD, McHale NG, Allen JM, Hughes G. 1990. Nerve-mediated contractions of sheep mesenteric lymph node capsules. J. Physiol. 422:513-22
127. Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD. 2001. The role of zinc in caspase activation and apoptotic cell death. Biometals 14:315-30
128. Vales-Gomez M, Erskine RA, Deacon MP, Strominger JL, Reyburn HT. 2001. The role of zinc in the binding of killer cell Ig-like receptors to class I MHC proteins. Proc. Natl. Acad. Sci. USA 98:1734-39
129. Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, et al. 2001. Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. J. Exp. Med. 193:497-507
130. von Bulow V, Dubben S, Engelhardt G, Hebel S, Plumakers B, et al. 2007. Zinc-dependent suppression of TNF-alpha production is mediated by protein kinase A-induced inhibition of Raf-1, I kappa B kinase beta, and NF-kappa B. J. Immunol. 179:4180-86
131. von Bulow V, Rink L, Haase H. 2005. Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF-alpha and IL-1 beta production in monocytes by elevation of guanosine 3′,5′- cyclic monophosphate. J. Immunol. 175:4697-705
132. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ. 2001. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346-51
133. Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J. 2002. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am. J. Hum. Genet. 71:66-73
134. Wellinghausen N, Martin M, Rink L. 1997. Zinc inhibits interleukin-1-dependent T cell stimulation. Eur. J. Immunol. 27:2529-35
135. Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, et al. 2004. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694-99
136. Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, et al. 2007. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol. Genomics 30:146-55
137. World Health Org. 2002. The World Health Report 2002. Geneva:World Health Org.
138. Wu W, Jaspers I, Zhang W, Graves LM, Samet JM. 2002. Role of Ras in metal-induced EGF receptor signaling and NF-kappaB activation in human airway epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 282:L1040-48
139. Wu W,Wang X, Zhang W, Reed W, Samet JM, et al. 2003. Zinc-induced PTEN protein degradation through the proteasome pathway in human airway epithelial cells. J. Biol. Chem. 278:28258-63
140. Yamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, et al. 2007. Zinc is a novel intracellular second messenger. J. Cell Biol. 177:637-45
141. Yoder JH, Chong H, Guan KL, Han M. 2004. Modulation of KSR activity in Caenorhabditis elegans by Zn ions, PAR-1 kinase and PP2A phosphatase. EMBO J. 23:111-19
142. Yokoyama WM, Plougastel BF. 2003. Immune functions encoded by the natural killer gene complex. Nat. Rev. Immunol. 3:304-16
143. Zalewski PD, Forbes IJ, Giannakis C, Cowled PA, Betts WH. 1990. Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton. FEBS Lett. 273:131-34
144. Zhang Y,Wang H, Li J, Dong L, Xu P, et al. 2006. Intracellular zinc release and ERK phosphorylation are required upstream of 12-lipoxygenase activation in peroxynitrite toxicity to mature rat oligodendrocytes. J. Biol. Chem. 281:9460-70