ADP-Ribosylation and CD38 Signaling



Mono-ADP-ribosylation is a posttranslational protein modification reaction that was originally discovered as a mechanism by which bacterial toxins interfere with signal transduction in human host cells [1, 2]. Mono-ADP-ribosylation is also used as a mechanism to regulate endogenous metabolism, as clearly demonstrated in photosynthetic bacteria [3]. Mammalian endogenous mono-ADP-ribosylation has also been studied and the responsible enzymes have been purified and defined at the molecular level [4–9].


Insulin Secretion Islet Cell CD38 Signaling Nicotinamide Adenine Dinucleotide Endocytic Vesicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ueda K. and Hayaishi O. 1985. ADP-ribosylation. Annu. Rev. Biochem. 54: 73–100.PubMedCrossRefGoogle Scholar
  2. 2.
    Wreggett KA. 1986. Bacterial toxins and the role of ADP-ribosylation. J. Recept. Res. 6: 95–126.PubMedGoogle Scholar
  3. 3.
    Ludden PW. 1994. Reversible ADP-ribosylation as a mechanism of enzyme regulation in procaryotes. Mol. Cell. Biochem. 138: 123–129.PubMedCrossRefGoogle Scholar
  4. 4.
    Yost DA and Moss J. 1983. Amino acid-specific ADP-ribosylation. Evidence for two distinct NAD:arginine ADP-ribosyltransferases in turkey erythrocytes. J. Biol. Chem. 258: 4926–4929.PubMedGoogle Scholar
  5. 5.
    Godeau F, Belin D, and Koide SS. 1984. Mono(adenosine diphosphate ribosyl) transferase in Xenopus tissues. Direct demonstration by a zymographic localization in sodium dodecyl sulfate-polyacrylamide gels. Anal. Biochem. 137: 287–296.PubMedCrossRefGoogle Scholar
  6. 6.
    Peterson JE, Larew JS and Graves DJ. 1990. Purification and partial characterization of arginine-specirlc ADP- ribosyltransferase from skeletal muscle microsomal membranes. J. Biol. Chem. 265: 17062–17069.PubMedGoogle Scholar
  7. 7.
    Maehama T, Takahashi K, Ohoka Y, Ohtsuka T, Ui M and Katada T. 1991. Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins. J. Biol. Chem. 266: 10062–10065.PubMedGoogle Scholar
  8. 8.
    Zolkiewska A, Nightingale MS and Moss J. 1992. Molecular characterization of NAD:arginine ADP-ribosyltransferase from rabbit skeletal muscle. Proc. Natl. Acad. Sci. USA 89: 11352–11356.PubMedCrossRefGoogle Scholar
  9. 9.
    Tsuchiya M, Hara N, Yamada K, Osago H and Shimoyama M. 1994. Cloning and expression of cDNA for arginine-specific ADP- ribosyltransferase from chicken bone marrow cells. J. Biol. Chem. 269: 27451–27457.PubMedGoogle Scholar
  10. 10.
    Wang J, Nemoto E, Kots AY, Kaslow HR and Dennert G. 1994. Regulation of cytotoxic T cells by ecto-nicotinamide adenine dinucleotide (NAD) correlates with cell surface GPI-anchored/arginine ADP-ribosyltransferase. J. Immunol. 153: 4048–4058.PubMedGoogle Scholar
  11. 11.
    Greiner DL, Mordes JP, Handler ES, Angelillo M, Nakamura N and Rossini AA. 1987. Depletion of RT6.T T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats. J. Exp. Med. 166: 461–475.PubMedCrossRefGoogle Scholar
  12. 12.
    Mehta K and Malavasi F. 2000. Human CD38 and related molecules, Chem. Immunol. 75, Karger, Basel, Switzerland.Google Scholar
  13. 13.
    Kim H. Jacobson EL and Jacobson MK. 1993. Synthesis and degradation of cyclic ADP-ribose by NAD glycohydrolases. Science 261. 1330–1333.PubMedCrossRefGoogle Scholar
  14. 14.
    Howard M, Grimaldi JC, Bazan JF, Lund FE, Santos-Argumedo L, Parkhouse RM, Walseth TF and Lee HC. 1993. Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science 262: 1056–1059.PubMedCrossRefGoogle Scholar
  15. 15.
    Zocchi E, Franco L, Guida L, Benatti U, Bargellesi A, Malavasi F, Lee HC and De Flora A. 1993. A single protein immunologically identified as CD38 displays NAD+ glycohydrolase. ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer surface of human erythrocytes. Biochem. Biophys. Res. Commun. 196: 1459–1465.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee HC. 1997. Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP. Physiol. Rev. 11: 1133–1164.Google Scholar
  17. 17.
    Wu Y, Kuzma J, Marechal E, Graeff R, Lee HC, Foster R and Chua NH. 1997. Abscisic acid signaling through cyclic ADP-ribose in plants. Science 278: 2126–2130.PubMedCrossRefGoogle Scholar
  18. 18.
    Takasawa S. Nata K. Yonekura H and Okamoto H. 1993. Cyclic ADP-ribose in insulin secretion from pancreatic beta cells. Science 259: 370–373.PubMedCrossRefGoogle Scholar
  19. 19.
    Liberman 1957. The mechanism of the specific depression of an enzyme activity in cells in tissue culture. J. Biol. Chem. 225: 883–898.Google Scholar
  20. 20.
    Green S and Dobrjansky A. 1971. pH-dependent inactivation of nicotinamide-adenine dinucleotide glycohydrolase by its substrate, oxidized nicotinamide-adenine dinucleotide. Biochemistry 10: 2496–2500.PubMedCrossRefGoogle Scholar
  21. 21.
    Han MK, Lee JY, Cho YS, Song YM, An NH, Kim HR and Kim UH. 1996. Regulation of NAD+ glycohydrolase activity by NAD+-dependent auto-ADP- ribosylation. Biochem. J. 318:903–908.PubMedGoogle Scholar
  22. 22.
    Han MK, Cho YS, Kim YS, Yim CY and Kim UH. 2000. Interaction of two classes of ADP-ribose transfer reactions in immune signaling. J. Biol. Chem. 275: 20799–20805.PubMedCrossRefGoogle Scholar
  23. 23.
    Franco L. Guida L, Bruzzone S. Zocchi E, Usai C and De Flora A. 1998. The transmembrane glycoprotein CD38 is a catalytically active transporter responsible for generation and influx of the second messenger cyclic ADP-ribose across membranes. FASEB J. 12: 1507–1520.PubMedGoogle Scholar
  24. 24.
    Franco L, Zocchi E, Usai C, Guida L, Bruzzone S, Costa A and De Flora A. 2001. Paracrine roles of NAD+ and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts. J. Biol. Chem. 276: 21642–21648.PubMedGoogle Scholar
  25. 25.
    Han MK, Kim SJ, Park YR, Shin YM, Park HJ, Park KJ, Park KH, Kim HK, Jang SI, An NH and Kim UH. 2002. Antidiabetic Effect of a Prodrug of Cysteine, L-2-Oxothiazolidine-4- carboxylic Acid, through CD38 Dimerization and Internalization. J. Biol. Chem. 277:5315–5321.PubMedCrossRefGoogle Scholar
  26. 26.
    Bruzzone S, Guida L, Zocchi E, Franco L and De Flora A. 2001. Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. FASEB J. 15: 10–12.PubMedGoogle Scholar
  27. 27.
    Kim UH, Kim MK, Kim JS, Han MK, Park BH and Kim HR. 1993. Purification and characterization of NAD glycohydrolase from rabbit erythrocytes. Arch. Biochem. Biophys. 305: 147–152.PubMedCrossRefGoogle Scholar
  28. 28.
    Santos-Argumedo L, Teixeira C, Preece G, Kirkham PA and Parkhouse RM. 1993. A B lymphocyte surface molecule mediating activation and protection from apoptosis via calcium channels. J. Immunol. 151:3119–3130.PubMedGoogle Scholar
  29. 29.
    Guse AH, da Silva CP, Berg I, Skapenko AL, Weber K, Heyer P, Hohenegger M, Ashamu GA. Schulze-Koops H, Potter BV and Mayr GW. 1999. Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose. Nature 398: 70–73.Google Scholar
  30. 30.
    An NH, Han MK, Urn C, Park BH, Park BJ, Kim HK and Kim UH. 2001. Significance of ecto-cyclase activity of CD38 in insulin secretion of mouse pancreatic islet cells. Biochem. Biophys. Res. Commun. 282: 781–786.PubMedCrossRefGoogle Scholar
  31. 31.
    Ikehata F, Satoh J, Nata K, Tohgo A, Nakazawa T, Kato I, Kobayashi S, Akiyama T, Takasawa S, Toyota T and Okamoto H. 1998. Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients. J. Clin. Invest. 102: 395–401.PubMedCrossRefGoogle Scholar
  32. 32.
    Yagui K, Shimada F, Mimura M, Hashimoto N, Suzuki Y, Tokuyama Y, Nata K, Tohgo A, Ikehata F, Takasawa S, Okamoto H, Makino H, Saito Y and Kanatsuka A. 1998. A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro. Diabetologia 41: 1024–1028.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Department of BiochemistryChonbuk National University Medical SchoolChonjuKorea
  2. 2.Department of Internal MedicineChonbuk National University Medical SchoolChonjuKorea
  3. 3.Institute for Medical SciencesChonbuk National University Medical SchoolChonjuKorea

Personalised recommendations