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 t...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-07, Vol.275 (27), p.20799-20805
Main Authors: Han, Myung-Kwan, Cho, Yee-Sook, Kim, Young Saeng, Yim, Chang-Yeol, Kim, Uh-Hyun
Format: Article
Language:English
Subjects:
Adenosine Diphosphate Ribose - analogs & derivatives
Adenosine Diphosphate Ribose - metabolism
ADP-ribose
ADP-ribosyl Cyclase
ADP-ribosyl Cyclase 1
Animals
Antigens, CD
Antigens, Differentiation - immunology
Apoptosis
Arginine - metabolism
Calcium - metabolism
CD38 antigen
Cell Line
Cyclic ADP-Ribose
Cysteine - metabolism
Flow Cytometry
Humans
Lymphocyte Activation
Membrane Glycoproteins
Mice
Mice, Inbred BALB C
NAD - metabolism
NAD+ Nucleosidase - immunology
Phosphatidylinositol Diacylglycerol-Lyase
Poly(ADP-ribose) Polymerases - immunology
Poly(ADP-ribose) Polymerases - metabolism
Signal Transduction
T-Lymphocytes - immunology
Transfection
Type C Phospholipases - metabolism
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Summary: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 Ca2+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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M001189200