Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose.
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Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose. / Guse, A H; Da Silva, C P; Berg, I; Skapenko, A L; Weber, K; Heyer, P; Hohenegger, M; Ashamu, G A; Schulze-Koops, H; Potter, B V; Mayr, Georg W.
In: NATURE, Vol. 398, No. 6722, 6722, 1999, p. 70-73.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose.
AU - Guse, A H
AU - Da Silva, C P
AU - Berg, I
AU - Skapenko, A L
AU - Weber, K
AU - Heyer, P
AU - Hohenegger, M
AU - Ashamu, G A
AU - Schulze-Koops, H
AU - Potter, B V
AU - Mayr, Georg W.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 398
SP - 70
EP - 73
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 6722
M1 - 6722
ER -
