Interaction of two classes of ADP-ribose transfer reactions in immune signaling.
CD38 is a bifunctional ectoenzyme predominantly expressed on hematopoietic cells where its expression correlates with differentiation and proliferation. The two enzyme activities displayed by CD38 are an ADP-ribosyl cyclase and a cyclic adenosine diphosphate ribose (cADPR) hydrolase that catalyzes the synthesis and hydrolysis of cADPR. T lymphocytes can be induced to express CD38 when activated with antibodies against specific antigen receptors. If the activated T cells are then exposed with NAD, cell death by apoptosis occurs. During the exposure of activated T cells to NAD, the CD38 is modified by ecto-mono-ADP-ribosyltransferases (ecto-mono-ADPRTs) specific for cysteine and arginine residues. Arginine-ADP-ribosylation results in inactivation of both cyclase and hydrolase activities of CD38, whereas cysteine-ADP-ribosylation results only in the inhibition of the hydrolase activity. The arginine-ADP-ribosylation causes a decrease in intracellular cADPR and a subsequent decrease in Ca(2+) influx, resulting in apoptosis of the activated T cells. Our results suggest that the interaction of two classes of ecto-ADP-ribose transfer enzymes plays an important role in immune regulation by the selective induction of apoptosis in activated T cells and that cADPR mediated signaling is essential for the survival of activated T cells.
Han
M K
MK
Department of Biochemistry and Department of Internal Medicine, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, Chonbuk 561-182, Korea.
Cho
Y S
YS
Kim
Y S
YS
Yim
C Y
CY
Kim
U H
UH
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D017209:Apoptosis; D001120:Arginine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D036563:Cyclic ADP-Ribose; D003545:Cysteine / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009243:NAD / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D001120:Arginine; D011065:Poly(ADP-ribose) Polymerases; D010738:Type C Phospholipases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D003545:Cysteine; D002118:Calcium