The lymphocyte surface antigen CD38 acts as a nicotinamide adenine dinucleotide glycohydrolase in human T lymphocytes.
The extracellular domain of the lymphocyte surface antigen CD38 has been recently shown to share a high sequence homology with a nicotinamide adenine dinucleotide (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod Aplysia (E. States, D.J., Walseth, T.F., Lee, H. C., Trends Biochem. Sci. 1992. 17:495). In agreement with this finding, we present here evidence that CD38-overexpressing T cells, such as human thymocytes and cells from the human HPB-ALL T cell line, exhibit a NAD(+)-hydrolyzing enzymatic activity present on the outer surface of the cell membrane. In contrast, T lymphocytes with relatively low levels of CD38 marker, such as the human Jurkat cell line, display a lower activity. This suggests a relationship between ecto-NAD+ glycohydrolase activity and CD38 expression, as confirmed here when comparing wild-type Jurkat cells and a Jurkat cell variant overexpressing the CD38 molecule. Moreover, CD38 immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase enzyme: it transforms NAD+ stoichiometrically into nicotinamide plus adenosine 5'-diphosphoribose. Altogether these results strongly support the assumption that CD38 is actually a lymphocyte-specific NAD(+)-hydrolyzing enzyme, a finding that give new prospects to understand the in vivo function of this cell membrane protein.
Gelman
L
L
Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS URA 625, Groupe Hospitalier Pitié-Salpétrière, Paris, France.
Deterre
P
P
Gouy
H
H
Boumsell
L
L
Debré
P
P
Bismuth
G
G
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002648:Child; D006026:Glycoside Hydrolases / Q000032:analysis*; D006801:Humans; D008562:Membrane Glycoproteins; D009243:NAD / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009243:NAD; D006026:Glycoside Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1