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Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose

Author

Listed:
  • Andreas H. Guse

    (Institute of Physiological Chemistry, University of Hamburg)

  • Cristina P. da Silva

    (Institute of Physiological Chemistry, University of Hamburg)

  • Ingeborg Berg

    (Institute of Physiological Chemistry, University of Hamburg)

  • Alla L. Skapenko

    (University of Erlangen-Nürnberg)

  • Karin Weber

    (Institute of Physiological Chemistry, University of Hamburg)

  • Petra Heyer

    (Institute of Physiological Chemistry, University of Hamburg)

  • Martin Hohenegger

    (Institute of Pharmacology, University of Vienna)

  • Gloria A. Ashamu

    (Wolfson Laboratory for Medicinal Chemistry, University of Bath)

  • Hendrik Schulze-Koops

    (University of Erlangen-Nürnberg)

  • Barry V. L. Potter

    (Wolfson Laboratory for Medicinal Chemistry, University of Bath)

  • Georg W. Mayr

    (Institute of Physiological Chemistry, University of Hamburg)

Abstract

Cyclic ADP-ribose (cADPR) is a natural compound that mobilizes calcium ions in several eukaryotic cells1,2,3. Although it can lead to the release of calcium ions in T lymphocytes4,5,6,7, it has not been firmly established as a second messenger in these cells. Here, using high-performance liquid chromatography analysis8, we show that stimulation of the T-cell receptor/CD3 (TCR/CD3) complex results in activation of a soluble ADP-ribosyl cyclase and a sustained increase in intracellular levels of cADPR. There is a causal relation between increased cADPR concentrations, sustained calcium signalling and activation of T cells, as shown by inhibition of TCR/CD3-stimulated calcium signalling, cell proliferation and expression of the early- and late-activation markers CD25 and HLA-DR by using cADPR antagonists9. The molecular target for cADPR, the type-3 ryanodine receptor/calcium channel, is expressed in T cells. Increased cADPR significantly and specifically stimulates the apparent association of [3H]ryanodine with the type-3 ryanodine receptor, indicating a direct modulatory effect of cADPR on channel opening. Thus we show the presence, causal relation and biological significance of the major constituents of the cADPR/calcium-signalling pathway in human T cells.

Suggested Citation

  • Andreas H. Guse & Cristina P. da Silva & Ingeborg Berg & Alla L. Skapenko & Karin Weber & Petra Heyer & Martin Hohenegger & Gloria A. Ashamu & Hendrik Schulze-Koops & Barry V. L. Potter & Georg W. May, 1999. "Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose," Nature, Nature, vol. 398(6722), pages 70-73, March.
    • Handle: RePEc:nat:nature:v:398:y:1999:i:6722:d:10.1038_18024
    DOI: 10.1038/18024
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