The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Zinc signals promote IL‐2‐dependent proliferation of T cells
Abstract
Zinc signals, i.e. a change of the intracellular concentration of free zinc ions in response to receptor stimulation, are involved in signal transduction in several immune cells. Here, the role of zinc signals in T‐cell activation by IL‐2 was investigated in the murine cytotoxic T‐cell line CTLL‐2 and in primary human T cells. Measurements with the fluorescent dyes FluoZin‐3 and Zinquin showed that zinc is released from lysosomes into the cytosol in response to stimulation of the IL‐2‐receptor. Activation of the ERK‐pathway was blocked by chelation of free zinc with N,N,N′,N′‐tetrakis‐2(pyridyl‐methyl)ethylenediamine, whereas zinc was not required for STAT5 phosphorylation. In addition, the key signaling molecules MEK and ERK were activated in response to elevated free intracellular zinc, induced by incubation with zinc and the ionophore pyrithione. Downstream of ERK activation, ERK‐specific gene expression of c‐fos and IL‐2‐induced proliferation was found to depend on zinc. Further experiments indicated that inhibition of MEK and ERK‐dephosphorylating protein phosphatases is the molecular mechanism for the influence of zinc on this pathway. In conclusion, an increase of cytoplasmic free zinc is required for IL‐2‐induced ERK signaling and proliferation of T cells.
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Cites
Malek, T. R. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090357 · Cited by 1,079
Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival
Junttila, M. R., Li, S., & Westermarck, J. (2008) · The FASEB Journal · doi:10.1096/fj.06-7859rev · Cited by 826
Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases
Owens, D. M., & Keyse, S. M. (2007) · Oncogene · doi:10.1038/sj.onc.1210412 · Cited by 777
Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208759 · Cited by 229
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Wessels, I., Maywald, M., & Rink, L. (2017) · Nutrients · doi:10.3390/nu9121286 · Cited by 747
Self-citationIon channels and transporters in lymphocyte function and immunity
Feske, S., Skolnik, E. Y., & Prakriya, M. (2012) · Nature Reviews Immunology · doi:10.1038/nri3233 · Cited by 441
The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis
Wessels, I., Rolles, B., & Rink, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01712 · Cited by 336
Self-citationMaywald, M., Wessels, I., & Rink, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102222 · Cited by 309
Metadata
- Authors
- Kaltenberg, J., Plum, L. M., Ober‐Blöbaum, J. L., Hönscheid, A., Rink, L., & Haase, H.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2010-04-29
- Volume
- 40
- Issue
- 5
- Pages
- 1496-1503
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1971861118
- Cited by
- 161
- References
- 4
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- closed
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