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28 March 2024 |
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Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose | A H Guse
; C P da Silva
; I Berg
; A L Skapenko
; K Weber
; P Heyer
; M Hohenegger
; G A Ashamu
; H Schulze-Koops
; B V Potter
; G W Mayr
; | Date: |
4 Mar 1999 | Journal: | Nature, 398 (6722), 70-3 | Abstract: | Cyclic ADP-ribose (cADPR) is a natural compound that mobilizes calcium ions in several eukaryotic cells. Although it can lead to the release of calcium ions in T lymphocytes, it has not been firmly established as a second messenger in these cells. Here, using high-performance liquid chromatography analysis, 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 antagonists. 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. | Source: | PubMed, pmid10078531 doi: 10.1038/18024 | Services: | Forum | Review | Favorites |
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