FEBS Letters | |
Hydrolysis of NADP+ by platelet CD38 in the absence of synthesis and degradation of cyclic ADP‐ribose 2′‐phosphate | |
Torti, Mauro2  Bertoni, Alessandra2  Canobbio, Ilaria2  Balduini, Cesare2  Sinigaglia, Fabiola1  | |
[1] Institute of Biological Chemistry, University of Genoa, viale Benedetto XV 1, 16132 Genoa, Italy;Department of Biochemistry, University of Pavia, via Bassi 21, 27100 Pavia, Italy | |
关键词: ADP-ribosyl cyclase; CD38; NADP+; Platelet; ADPR; ADP-ribose; cADPR; cyclic ADP-ribose; 2′-P-ADPR; ADP-ribose 2′-phosphate; 2′-P-cADPR; cyclic ADP-ribose 2′-phosphate; IP3; inositol 1; 4; 5-trisphosphate; | |
DOI : 10.1016/S0014-5793(99)00913-8 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
CD38 is a multifunctional cell surface ectoenzyme that catalyzes both the synthesis of cyclic ADP-ribose from NAD+ and its hydrolysis to ADP-ribose. In this work, we investigated the metabolism of NADP+ by CD38 expressed on human platelets. Incubation of either platelet membranes or intact cells with NADP+ resulted in the rapid and time-dependent accumulation of ADP-ribose 2′-phosphate that paralleled the consumption of the substrate. However, under the same conditions, synthesis of cyclic ADP-ribose 2′-phosphate was not observed. By immunoprecipitation experiments, we identified CD38 as the enzyme responsible for the observed NADP+ glycohydrolase activity. The lack of detection of cyclic ADP-ribose 2′-phosphate was not due to its rapid hydrolysis, since direct incubation of platelet membranes with cyclic ADP-ribose 2′-phosphate did not result in the formation of ADP-ribose 2′-phosphate. By contrast, the same membrane samples expressed a significant ability to hydrolyze cyclic ADP-ribose to ADP-ribose. The absence of cyclic ADP-ribose 2′-phosphate hydrolase activity was also confirmed using high concentrations of substrate and by analysing both intact Jurkat T-lymphocytes and immunoprecipitated CD38. These results indicate that CD38, which is a multifunctional enzyme towards NAD+, displays exclusively a NADP+ glycohydrolase activity and is unable to catalyze both the synthesis and the hydrolysis of cyclic ADP-ribose 2′-phosphate.
【 授权许可】
Unknown
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