generation of CD38(-/-) knockout mice of determine the role of this enzyme
calcium signaling messengers nicotinate-adenine dinucleotide phosphate and 2'-phospho-cyclic ADP-ribose are not produced when lymphokine-activated killer cells prepared from CD38 knock-out mice are treated with interleukin IL-8. Application of 2'-phospho-cyclic ADP-ribose to lymphikine-activated killer cells induces nicotinate-adenine dinucleotide phosphate production, whereas nicotinate-adenine dinucleotide phosphate fails to increase intracellular 2'-phospho-cyclic ADP-ribose levels. IL-8-induced nicotinate-adenine dinucleotide phosphate production is mediated by CD38 activation through the actions of cAMP/Epac/protein kinaseA/Rap1 in lymphokine-activated killer cells and nicotinate-adenine dinucleotide phosphate plays a key role in Ca2+ signaling of IL-8-induced lymphokine-activated killer cell migration.
gene silencing of CD38 does not inhibit NAADP synthesis in intact Jurkat T cells. In vitro, both NAADP formation by base-exchange and degradation to 2-phospho adenosine diphosphoribose are efficiently decreased. Thus in vivo CD38 appears to be a NAADP degrading rather than a NAADP forming enzyme
gene silencing of CD38 does not inhibit NAADP synthesis in thymus or spleen obtained from CD38 knock out mice
the enzyme is involved in synthesis of nicotinic acid-adenine dinucleotide phosphate, a calcium messenger that can mobilize intracellular Ca2+ stores and activate Ca2+ influx to regulate a wide range of physiological processes