Hydrolysis of NADP+ by platelet CD38 in the absence of synthesis and degradation of cyclic ADP‐ribose 2′‐phosphate

FEBS Letters

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