Murine CD38: an immunoregulatory ectoenzyme

Lund, Frances E.; Solvason, Nanette; Grimaldi, J. Christopher; Michael, R.; Parkhouse, R. M. E.; Howard, Maureen

doi:10.1016/0167-5699(95)80029-8

Cited by 98 publications

(62 citation statements)

References 44 publications

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“…This possibility would make it possible to reconcile the topological paradox of ectocellular localization of CD38 and intracellular site of action of its enzymatic product cADPR as a calcium mobilizer. Although, as pointed out in [2], endocytosis is expected to position the internalized CD38 within a membrane-bound intracellular vesicle (Fig. 3c,d), this seems to be accessible to cytosolic NAD +, as shown by the increase in cADPR levels.…”

Section: Discussionmentioning

confidence: 52%

“…3c,d), this seems to be accessible to cytosolic NAD +, as shown by the increase in cADPR levels. It has been speculated that extracellular NAD + might become available to CD38 + lymphoid cells, even at transiently elevated concentrations, following apoptosis of neighboring cells [1,2]. Recently, NAD + has been detected for the first time in the interstitial fluid of rat cerebellum [15], thus adding to ATP [33] as a previously unidentified extracellular signal metabolite.…”

Section: Discussionmentioning

confidence: 99%

“…Abbreviations: cADPR, cyclic ADP-ribose; ADPR, ADP-ribose; BSA, bovine serum albumin; NGD +, nicotinamide guanine dinucleotide; cGDPR, cyclic GDP-ribose; RIA, radioimmunoassay A major, still unresolved question on the CD38-cADPR system concerns the apparent contradiction between the ectocellular site of CD38-catalyzed production of cADPR and its intracellular calcium-mobilizing activity [2,11,13,14]. Neither cADPR influx across the plasma membrane nor cADPR-initiated signal transduction in responsive cells has been demonstrated so far, although external cADPR has been reported to enhance the proliferation of activated murine B lymphocytes [4].…”

Section: *Corresponding Author Fax: (39) (10) 354415mentioning

confidence: 99%

“…CD38 is a type II transmembrane glycoprotein predominantly expressed in early and late stages of lymphocyte development [1,2]. Its involvement in many processes of lymphocyte proliferation and differentiation as a receptor for still unidentified ligand(s) is supported by a wide range of effects on lymphocyte physiology elicited by ligation of CD38 with specific monoclonal antibodies (MoAbs) [1,2].…”

Section: Introductionmentioning

confidence: 99%

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NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

Zocchi¹,

Franco²,

Guida³

et al. 1996

FEBS Letters

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CD38 is a transmembrane glycoprotein involved as an orphan receptor in many physiological processes of lymphocytes. It is also a bifunctional enzyme that catalyzes at its ectocellular domain the synthesis from NAD + (cyclase) and the hydrolysis (hydrolase) of the calcium-mobilizing metabolite cyclic ADPribose (cADPR). A still unexplained paradox concerns the relationship between ectocellular localization of CD38 and intracellular calcium-releasing activity of its intermediate product cADPR. Incubation of CD38 + human Namalwa B cells with external NAD + elicited extensive membrane down-regulation of CD38 and its internalization in non-clathrin-coated vesicles. Since the internalized CD38 was demonstrated to be enzymatically active, this NAD+-dependent process is a hitherto unrecognized means for shifting cADPR metabolism from the cell surface to the intracellular environment.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: *Corresponding Author Fax: (39) (10) 354415mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

Zocchi¹,

Franco²,

Guida³

et al. 1996

FEBS Letters

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“…CD38 is expressed on the cell surfaces of a wide variety of cells, including B and T lymphocytes, NK cells, macrophages, [34] and even on islet cells [35]. It functions mainly as an NAD hydrolase with some ADP-ribosyl cyclase activity.…”

Section: Discussionmentioning

confidence: 99%

Changing patterns of cell surface mono (ADP-ribosyl) transferase antigen ART2.2 on resting versus cytopathically-activated T cells in NOD/Lt mice

Ablamunits

Bridgett²,

Duffy

et al. 2001

Diabetologia

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Mouse Chromosome 7 contains a cluster of genes encoding functional mono ADP-ribosyltransferases (ART) expressed on the surface of T cells [1]. These enzymes are capable of catalyzing the hydrolysis of nicotine adenine dinucleotide (NAD) into ADP-ribose and nicotinamide [2], and the transfer of the ADP-ribose moiety onto arginine residues of T-cell surface molecules associated with transmission of activation signals or with adherence [3]. One of these genes, designated Art1, was initially cloned from YAC1 cells and represents a mouse ortholog of a gene cloned from rabbit skeletal muscle [4]. A tandem duplication of another mouse Art gene tightly linked to Art1 and now designated Art 2 a and Art2 b represents mouse orthologs of the single rat gene en- Abstract Aims/hypothesis. ART2.2 is a mouse T-cell surface ectoenzyme [mono (ADP-ribosyl) transferase] shed upon strong activation. We analysed temporal changes in ART2.2 expression in unmanipulated and cyclophosphamide-treated NOD/Lt mice compared with diabetes-resistant control strains. We used NAD, the ART2.2 substrate, to test whether ARTmediated ADP-ribosylation could retard diabetogenic activation of islet-reactive T cells in vitro. Methods. ART2.2 and CD38, another NAD-utilizing enzyme, were measured by flow cytometry. ADP-ribosylation from ethano-NAD was followed by flow cytometry using a reagent specific for etheno-ADP ribose. Results. Although mature NOD CD4 + and C D8 + T cells expressed ART2.2, this expression was delayed in young NOD mice when compared with control strains. This ontological delay at 3 weeks of age correlated with an early burst of CD25 expression unique to NOD splenic T cells. This pattern was reproduced in cyclophosphamide-accelerated diabetes in young NOD/Lt males, wherein a retarded repopulation of ART2.2 T cells in spleen and islets correlated with development of heavy insulitis and diabetes. NAD inhibited anti-CD3 induced activation of splenic T cells in vitro and also retarded killing of beta-cell targets by NOD islet-reactive CD8 effectors in vitro at concentrations equal to or greater than 1 mmol/l. Evidence suggested that CD38 on B lymphocytes competes with ART2.2 for substrate needed by B lymphocytes for ADP ribosylation. Conclusions. ART2.2 on T cells may not simply mark the resting state, but could also contribute to it via ADP-ribosylation. [Diabetologia (2001) 44: 848±858]

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Extracellular purine metabolism

1996

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Murine CD38: an immunoregulatory ectoenzyme

Cited by 98 publications

References 44 publications

NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

Changing patterns of cell surface mono (ADP-ribosyl) transferase antigen ART2.2 on resting versus cytopathically-activated T cells in NOD/Lt mice

Extracellular purine metabolism

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Murine CD38: an immunoregulatory ectoenzyme

Cited by 98 publications

References 44 publications

NAD+‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

NAD+‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

Changing patterns of cell surface mono (ADP-ribosyl) transferase antigen ART2.2 on resting versus cytopathically-activated T cells in NOD/Lt mice

Extracellular purine metabolism

Contact Info

Product

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NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells

NAD⁺‐dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells