Skip to main content
SpringerLink
Log in

A Natural History of the Human CD38 Gene

  • Chapter
Cyclic ADP-Ribose and NAADP

Abstract

In the beginning, CD38 (gene symbol CD38) was but one of a handful of thymic lymphocyte surface markers [1]. It was subsequently found to be expressed also by B cells, monocytes and natural killer cells, as detailed in [2]. In immunocytes, it emerged that engagement of CD38 by specific monoclonal antibodies could command a variety of responses such as activation and cytokine release in T cells [3, 4], modulation of B cell antigen receptor responses [4], B and myeloid cell apoptosis [6, 7], modulation of the superantigen response in monocytes [7] and induction of NK cell activation and cytotoxicity [9, 10]. In addition, CD38 can influence immunocyte adhesion to endothelium [10] through a counterreceptor identified as CD31 [11], leaving no doubts about the receptorial nature of CD38. The intracellular pathways activated via CD38 are being characterized and numerous cytoplasmic substrates have been identified that undergo phosphorylation following CD38 signaling [12, 16].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Reinherz EL, Kung PC, Goldstein G, Levey RH and Schlossman SF. 1980. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc. Natl. Acad. Sci. USA 11: 1588–1592.

    Article  Google Scholar 

  2. Malavasi F, Funaro A, Alessio M, DeMonte LB, Ausiello CM, Dianzani U, Lanza F, Magrini E, Momo M and Roggero S. 1992. CD38: a multi-lineage cell activation molecule with a split personality. Int. J. Clin. Lab. Res. 22: 73–80.

    Article  PubMed  CAS  Google Scholar 

  3. Funaro A, Spagnoli GC, Ausiello CM, Alessio M, Roggero S, Delia D, Zaccolo M and Malavasi F. 1990. Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. J. Immunol. 145: 2390–2396.

    PubMed  CAS  Google Scholar 

  4. Lund FE, Yu N, Kim KM, Reth M and Howard MC. 1996. Signaling through CD38 augments B cell antigen receptor (BCR) responses and is dependent on BCR expression. J. Immunol. 157: 1455–1467.

    PubMed  CAS  Google Scholar 

  5. Zupo S, Rugari E, Dono M, Taborelli G, Malavasi F and Ferrarini M. 1994. CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells. Eur. J. Immunol. 24: 1218–1222.

    Article  PubMed  CAS  Google Scholar 

  6. Kumagai M, Coustan-Smith E, Murray DJ, Silvennoinen O, Murti KG, Evans WE, Malavasi F and Campana D. 1995. Ligation of CD38 suppresses human B lymphopoiesis. J. Exp. Med. 181: 1101–1110.

    Article  PubMed  CAS  Google Scholar 

  7. Zilber MT, Gregory S, Mallone R, Deaglio S, Malavasi F, Charron D and Gelin C. 2000. CD38 expressed on human monocytes: a coaccessory molecule in the superantigen-induced proliferation. Proc. Natl. Acad. Sci. USA 97: 2840–2845.

    Article  PubMed  CAS  Google Scholar 

  8. Mallone R, Funaro A, Zubiaur M, Baj G, Ausiello CM, Tacchetti C, Sancho J, Grossi C and Malavasi F. 2001. Signaling through CD38 induces NK cell activation. Int. Immunol. 13:397–409.

    Article  PubMed  CAS  Google Scholar 

  9. Sconocchia G, Titus JA, Mazzoni A, Visintin A, Pericle F, Hicks SW, Malavasi F and Segal DM. 1999. CD38 triggers cytotoxic responses in activated human natural killer cells. Blood 94: 3864–3871.

    PubMed  CAS  Google Scholar 

  10. Dianzani U, Funaro A, DiFranco D, Garbarino G, Bragardo M, Redoglia V, Buonfiglio D and De Monte LB, Pileri A and Malavasi F. 1994. Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule. J. Immunol. 153: 952–959.

    PubMed  CAS  Google Scholar 

  11. Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, Dianzani U, Stockinger H and Malavasi F. 1998. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31. an Ig superfamily member. J. Immunol. 160: 395–402.

    PubMed  CAS  Google Scholar 

  12. Kikuchi Y, Yasue T, Miyake K, Kimoto M and Takatsu K. 1995. CD38 ligation induces tyrosine phosphorylation of Bruton tyrosine kinase and enhanced expression of interleukin 5-receptor alpha chain: synergistic effects with interleukin 5. Proc. Natl. Acad. Sci. USA 92: 11814–11818.

    Article  PubMed  CAS  Google Scholar 

  13. Silvennoinen O, Nishigaki H, Kitanaka A, Kumagai M, Ito C, Malavasi F, Lin Q, Conley ME and Campana D. 1996. CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase C-gamma and phosphatidylinositol 3- kinase. J. Immunol. 156: 100–107.

    PubMed  CAS  Google Scholar 

  14. Zubiaur M, Izquierdo M, Terhorst C, Malavasi F and Sancho J. 1997. CD38 ligation results in activation of the Raf-1/mitogen-activated protein kinase and the CD3-zeta/zeta-associated protein-70 signaling pathways in Jurkat T lymphocytes. J. Immunol. 159: 193–205.

    PubMed  CAS  Google Scholar 

  15. Inoue S, Kontani K, Tsujimoto N, Kanda Y, Hosoda N, Hoshino S, Hazeki O and Katada T. 1997. Protein-tyrosine phosphorylation by IgGl subclass CD38 monoclonal antibodies is mediated through stimulation of the Fc-gamma-II receptors in human myeloid cell lines. J. Immunol. 159: 5226–5232.

    PubMed  CAS  Google Scholar 

  16. Yasue T, Nishizumi H, Aizawa S, Yamamoto T, Miyake K, Mizoguchi C, Uehara S, Kikuchi Y and Takatsu K. 1997. A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5. Proc. Natl. Acad. Sci. USA 94: 10307–10312.

    Article  PubMed  CAS  Google Scholar 

  17. States DJ, Walseth TF and Lee HC. 1992. Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38. Frends Biochem.Sci 17: 495.

    Article  CAS  Google Scholar 

  18. Lee HC. 2001. Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers. Annu. Rev. Pharmacol. Toxicol. 41: 317–345.

    Article  PubMed  Google Scholar 

  19. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP and Scharenberg AM. 2001. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411: 595–599.

    Article  PubMed  CAS  Google Scholar 

  20. Koch-Nolte F, Reche P, Haag F and Bazan F. 2001. ADP-ribosyltransferases: plastic tools for inactivating protein and small molecular weight targets. J. Biotechnol. 92: 81–87.

    Article  PubMed  CAS  Google Scholar 

  21. Okamoto H, Takasawa S, Nata K, Kato I, Tohgo A and Noguchi N. 2000. Physiological and pathological significance of the CD38/cyclic ADP-ribose signaling system. Chem. Immunol. 75: 121–145.

    Article  PubMed  CAS  Google Scholar 

  22. Partida-Sanchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B, Kusser K, Goodrich S, Howard M, Harmsen A, Randall TD and Lund FE. 2001. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nature Med. 7: 1209–1216.

    Article  PubMed  CAS  Google Scholar 

  23. Rosengren E, Aman P, Thelin S, Hansson C, Ahlfors S, Bjork P, Jacobsson L and Rorsman H. 1997. The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase. FEBS Lett. 417: 85–88.

    Article  PubMed  CAS  Google Scholar 

  24. Nakagawara K, Mori M, Takasawa S, Nata K, Takamura T, Berlova A, Tohgo A, Karasawa T. Yonekura H. Takeuchi T, et al. 1995. Assignment of CD38, the gene encoding human leukocyte antigen CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase), to chromosome 4pl5. Cytogenet. Cell Genet. 69: 38–39.

    Article  PubMed  CAS  Google Scholar 

  25. Nata K, Takamura T, Karasawa T, Kumagai T, Hashioka W, Tohgo A, Yonekura H, Takasawa S, Nakamura S and Okamoto H. 1997. Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing. Gene 186: 285–292.

    Article  PubMed  CAS  Google Scholar 

  26. Landsman D, Soares N, Gonzalez FJ and Bustin M. 1986. Chromosomal protein HMG-17. Complete human cDNA sequence and evidence for a multigene family. J. Biol. Chem. 261:7479–7484.

    PubMed  CAS  Google Scholar 

  27. Okamoto T, Tanaka Y, Kan M, Sakamoto A, Takada K and Sato JD. 1996. Expression of fibroblast growth factor binding protein HBpl7 in normal and tumor cells. In Vitro Cell Dev. Biol. Anim. 32:69–71.

    Article  PubMed  CAS  Google Scholar 

  28. Ogawa K, Tanaka K, Ishii A, Nakamura Y, Kondo S, Sugamura K, Takano S, Nakamura M and Nagata K. 2001. A novel serum protein that is selectively produced by cytotoxic lymphocytes. J. Immunol. 166: 6404–6412.

    PubMed  CAS  Google Scholar 

  29. Kratz-Albers K, Zuhlsdorp M, Leo R, Berdel WL, Buchner T and Serve H. 1998. Expression of a AC 133, a novel stem cell marker, on human leukemic blasts lacking CD34-antigen and on a human CD34+ leukemic line: MUTZ-2. Blood 92: 4485–4487.

    PubMed  CAS  Google Scholar 

  30. Ortolan E, Capobianco A, Armando E, Crivellin F, Horenstein A and Malavasi F. 2002. CD 157, the Janus of CD38 but with a unique personality. Cell Biochem. Funct. 20: 1–14.

    Article  CAS  Google Scholar 

  31. Terstappen LW, Huang S, Safford M, Lansdorp PM and Loken MR. 1991. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34-TD38- progenitor cells. Blood 77: 1218–1227.

    PubMed  CAS  Google Scholar 

  32. Jackson DG and Bell JI. 1990. Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. J. Immunol. 144: 2811–2815.

    PubMed  CAS  Google Scholar 

  33. Alessio M, Roggero S, Funaro A, De Monte LB, Peruzzi L, Geuna M and Malavasi F. 1990. CD38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells. J. Immunol. 145: 878–884.

    PubMed  CAS  Google Scholar 

  34. Ferrero E and Malavasi F. 1997. Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase. J. Immunol. 159: 3858–3865.

    PubMed  CAS  Google Scholar 

  35. Funaro A, Horenstein AL, Calosso L, Morra M, Tarocco RP, Franco L, De Flora A and Malavasi F. 1996. Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids. Int. Immunol. 8: 1643–1650.

    Article  PubMed  CAS  Google Scholar 

  36. Yamauchi J and Tanuma S. 1994. Occurrence of an NAD+ glycohydrolase in bovine brain cytosol. Arch. Biochem. Biophys. 308: 327–329.

    Article  CAS  Google Scholar 

  37. Moser B, Winterhalter KH and Richter C. 1983. Purification and properties of a mitochondrial NAD+ glycohydrolase. Arch. Biochem. Biophys. 224: 358–364.

    Article  PubMed  CAS  Google Scholar 

  38. Khoo KM and Chang CF. 2002. Identification and characterization of nuclear CD38 in the rat spleen. Int. J. Biochem. Cell Biol. 34: 43–54.

    Article  PubMed  CAS  Google Scholar 

  39. Fernandez JE, Deaglio S, Donati D, Beusan IS, Corno F, Aranega A, Forni M, Falini B and Malavasi F. 1998. Analysis of the distribution of human CD38 and of its ligand CD31 in normal tissues. J. Biol. Regul. Homeost. Agents 12: 81–91.

    PubMed  CAS  Google Scholar 

  40. Kishimoto H, Hoshino S, Ohori M, Kontani K, Nishina H, Suzawa M, Kato S and Katada T. 1998. Molecular mechanism of human CD38 gene expression by retinoic acid. Identification of retinoic acid response element in the first intron. J. Biol. Chem. 273: 15429–15434.

    Article  PubMed  CAS  Google Scholar 

  41. Ernst P and Smale ST. 1995. Combinatorial regulation of transcription. I: General aspects of transcriptional control. Immunity 2: 311–9.

    Article  PubMed  CAS  Google Scholar 

  42. Chini EN, de Toledo FG, Thompson MA and Dousa TP. 1997. Effect of estrogen upon cyclic ADP ribose metabolism: beta-estradiol stimulates ADP ribosyl cyclase in rat uterus. Proc. Natl. Acad. Sci. USA 94: 5872–5876.

    Article  PubMed  CAS  Google Scholar 

  43. Funaro A, Ferrero E, Mehta K and Malavasi F. 2000. Schematic portrait of human CD38 and related molecules. Chem. Immunol. 75: 256–273.

    Article  PubMed  CAS  Google Scholar 

  44. Tennyson CN, Klamut HJ and Worton RG. 1995. The human dystrophin gene requires 16 hours to be transcribed and is contranscriptionally spliced. Nature Genet. 9: 184–190.

    Article  PubMed  CAS  Google Scholar 

  45. Ferrero E, Saccucci F and Malavasi F. 1999. The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene. Immunogenet. 49: 597–604.

    Article  CAS  Google Scholar 

  46. Mallone R, Ortolan E, Baj G, Funaro A, Giunti S, Lillaz E, Saccucci F, Cassader M, Cavallo-Perin P and Malavasi F. 2001. Autoantibody response to CD38 in Caucasian patients with type 1 and type 2 diabetes: immunological and genetic characterization. Diabetes 50: 752–762.

    Article  PubMed  CAS  Google Scholar 

  47. Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G and Groves CP. 1998. Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence. Mol. Phylogenet. Evol. 9: 585–598.

    Article  PubMed  CAS  Google Scholar 

  48. Muraoka O, Tanaka H, Itoh M, Ishihara K and Hirano T. 1996. Genomic structure of human BST-1. Immunol. Lett. 54: 1–4.

    Article  PubMed  CAS  Google Scholar 

  49. Nata K, Sugimoto T, Tohgo A, Takamura T, Noguchi N, Matsuoka A, Numakunai T, Shikama K, Yonekura H, Takasawa S. et al. 1995. The structure of the Aplysia kurodai gene encoding ADP-ribosyi cyclase, a second-messenger enzyme. Gene 158: 213–218.

    Article  PubMed  CAS  Google Scholar 

  50. Glick DL, Hellmich MR, Beushausen S, Tempst P, Bayley H and Strumwasser F. 1991. Primary structure of a molluscan egg-specific NADase, a second-messenger enzyme. Cell Regul. 2:211–218.

    PubMed  CAS  Google Scholar 

  51. Graeff R, Munshi C, Aarhus R, Johns M and Lee HC. 2001. A single residue at the active site of CD38 determines its NAD cyclizing and hydrolyzing activities. J. Biol. Chem. 276: 12169–12173.

    Article  PubMed  CAS  Google Scholar 

  52. Munshi C, Aarhus R, Graeff R, Walseth TF, Levitt D and Lee HC. 2000. Identification of the enzymatic active site of CD38 by site-directed mutagenesis. J. Biol. Chem. 275: 21566–21571.

    Article  PubMed  CAS  Google Scholar 

  53. Ferrero E and Malavasi F. 1999. The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38. J. Leukoc. Biol. 65: 151–161.

    PubMed  CAS  Google Scholar 

  54. Morra M, Zubiaur M, Terhorst C, Sancho J and Malavasi F. 1998. CD38 is functionally dependent on the TCR/CD3 complex in human T cells. FASEB J. 12: 581–592.

    PubMed  CAS  Google Scholar 

  55. Deaglio SZM, Gregorini A, Bottarel, Ausiello C, Dianzani U, Sancho J and Malavasi F. 2002. Human CD38 and CD 16 are functionally dependent and physicaly associated in natural killer cells. Blood 90: (in press).

    Google Scholar 

  56. Cockayne DA, Muchamuel T, Grimaldi JC, Muller-Steffner H, Randall TD, Lund FE, Murray R, Schuber F and Howard MC. 1998. Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood 92: 1324–1333.

    PubMed  CAS  Google Scholar 

  57. Kato I, Yamamoto Y, Fujimura M, Noguchi N, Takasawa S, Okamoto H. 1999. CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion. J. Biol. Chem. 274: 1869–1872.

    Article  PubMed  CAS  Google Scholar 

  58. Hamblin TJ, Orchard JA, Ibbotson RE, Davis Z, Thomas PW, Stevenson FK and Oscier DG. 2002. CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood 99: 1023–1029.

    Article  PubMed  CAS  Google Scholar 

  59. Mehta K. 2000. Retinoid-mediated signaling in CD38 antigen expression. Chem. Immunol. 75: 20–38.

    Article  PubMed  CAS  Google Scholar 

  60. Kramer G, Steiner G, Fodinger D, Fiebiger E, Rappersberger C, Binder S, Hofbauer J and Marberger M. 1995. High expression of a CD38-like molecule in normal prostatic epithelium and its differential loss in benign and malignant disease. J. Urol. 154: 1636–1641.

    Article  PubMed  CAS  Google Scholar 

  61. Savarino A, Bottarel F, Malavasi F and Dianzani U. 2000. Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an active player in virus/host interactions? AIDS 14: 1079–1089.

    Article  PubMed  CAS  Google Scholar 

  62. 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.

    Article  PubMed  CAS  Google Scholar 

  63. Pupilli C, Giannini S, Marchetti P, Lupi R, Antonelli A, Malavasi F, Takasawa S, Okamoto H and Ferrannini E. 1999. Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes: effects on insulin release from human islets. Diabetes 48: 2309–2315.

    Article  PubMed  CAS  Google Scholar 

  64. Antonelli A, Fallahi P, Nesti C, Pupilli C, Marchetti P, Takasawa S, Okamoto H and Ferrannini E. 2001. Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves’ disease. Clin. Exp. Immunol. 126: 426–431.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Immunogenetics, S. Giovanni Battista Hospital, Turin, Italy

    Enza Ferrero MD & Fabio Malavasi

  2. Department of Genetics, Biology and Biochemistry, S. Giovanni Battista Hospital, Via Santena, 19, 10126, Torino, Italy

    Enza Ferrero MD & Fabio Malavasi

  3. Faculty of Medicine, University of Turin and Experimental Medicine Research Center, S. Giovanni Battista Hospital, Turin, Italy

    Enza Ferrero MD & Fabio Malavasi

Authors
  1. Enza Ferrero MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabio Malavasi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Minneapolis, USA

    Hon Cheung Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ferrero, E., Malavasi, F. (2002). A Natural History of the Human CD38 Gene. In: Lee, H.C. (eds) Cyclic ADP-Ribose and NAADP. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0269-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0269-2_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4996-9

  • Online ISBN: 978-1-4615-0269-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation