HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Flora, A. Articles by Lee, H. C. Search for Related Content PubMed PubMed Citation Articles by De Flora, A. Articles by Lee, H. C. Social Bookmarking                      What's this?

Volume 272, Number 20, Issue of May 16, 1997 pp. 12945-12951
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

CD38 and ADP-ribosyl Cyclase Catalyze the Synthesis of a Dimeric ADP-ribose That Potentiates the Calcium-mobilizing Activity of Cyclic ADP-ribose

(Received for publication, November 19, 1996, and in revised form, February 19, 1997)

Antonio De Flora , Lucrezia Guida , Luisa Franco ^¶ , Elena Zocchi , Santina Bruzzone , Umberto Benatti , Gianluca Damonte and Hon Cheung Lee ^¶

From the  Institute of Biochemistry, University of Genova, 16132 Genova, Italy and the ^¶ Department of Physiology, University of Minnesota, Minneapolis, Minnesota 55455

CD38, a lymphocyte differentiation antigen, is also a bifunctional enzyme catalyzing the synthesis of cyclic ADP-ribose (cADPR) from NAD⁺ and its hydrolysis to ADP-ribose (ADPR). An additional enzymatic activity of CD38 shared by monofunctional ADP-ribosyl cyclase from Aplysia californica is the exchange of the base group of NAD⁺ (nicotinamide) with various nucleophiles. Both human CD38 (either recombinant or purified from erythrocyte membranes) and Aplysia cyclase were found to catalyze the exchange of ADPR with the nicotinamide group of NAD⁺ leading to the formation of a dimeric ADPR ((ADPR)₂). The dimeric structure of the enzymatic product, which was generated by recombinant CD38 and by CD38⁺ Namalwa cells from as low as 10 µM NAD⁺, was demonstrated using specific enzyme treatments (dinucleotide pyrophosphatase and 5-nucleotidase) and mass spectrometry analyses of the resulting products. The linkage between the two ADPR units of (ADPR)₂ was identified as that between the N¹ of the adenine nucleus of one ADPR unit and the anomeric carbon of the terminal ribose of the second ADPR molecule by enzymatic analyses and by comparison with patterns of cADPR cleavage with Me₂SO:tert-butoxide. Although (ADPR)₂ itself did not release Ca²⁺ from sea urchin egg microsomal vesicles, it specifically potentiated the Ca²⁺-releasing activity of subthreshold concentrations of cADPR. Therefore, (ADPR)₂ is a new product of CD38 that amplifies the Ca²⁺-mobilizing activity of cADPR.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF]

				S. Bruzzone, G. Dodoni, N. Kaludercic, G. Basile, E. Millo, A. De Flora, F. Di Lisa, and E. Zocchi Mitochondrial Dysfunction Induced by a Cytotoxic Adenine Dinucleotide Produced by ADP-ribosyl Cyclases from cADPR J. Biol. Chem., February 16, 2007; 282(7): 5045 - 5052. [Abstract] [Full Text] [PDF]

				P. Palade The hunt for an alternate way to generate NAADP. Focus on "NAADP as a second messenger: neither CD38 nor base-exchange reaction are necessary for in vivo generation of NAADP in myometrial cells" Am J Physiol Cell Physiol, January 1, 2007; 292(1): C4 - C7. [Full Text] [PDF]

				Q. Liu, I. A. Kriksunov, R. Graeff, C. Munshi, H. C. Lee, and Q. Hao Structural Basis for the Mechanistic Understanding of Human CD38-controlled Multiple Catalysis J. Biol. Chem., October 27, 2006; 281(43): 32861 - 32869. [Abstract] [Full Text] [PDF]

				L. Sternfeld, E. Krause, A. H. Guse, and I. Schulz Hormonal Control of ADP-ribosyl Cyclase Activity in Pancreatic Acinar Cells from Rats J. Biol. Chem., September 5, 2003; 278(36): 33629 - 33636. [Abstract] [Full Text] [PDF]

				L. Sun, O. A. Adebanjo, B. S. Moonga, S. Corisdeo, H. K. Anandatheerthavarada, G. Biswas, T. Arakawa, Y. Hakeda, A. Koval, B. Sodam, et al. CD38/ADP-Ribosyl Cyclase: A New Role in the Regulation of Osteoclastic Bone Resorption J. Cell Biol., September 6, 1999; 146(5): 1161 - 1172. [Abstract] [Full Text] [PDF]

				F. E. Lund, H. M. Muller-Steffner, N. Yu, C. D. Stout, F. Schuber, and M. C. Howard CD38 Signaling in B Lymphocytes Is Controlled by Its Ectodomain but Occurs Independently of Enzymatically Generated ADP-Ribose or Cyclic ADP-Ribose J. Immunol., March 1, 1999; 162(5): 2693 - 2702. [Abstract] [Full Text] [PDF]

				A. Kitanaka, T. Suzuki, C. Ito, H. Nishigaki, E. Coustan-Smith, T. Tanaka, Y. Kubota, and D. Campana CD38-Mediated Signaling Events in Murine Pro-B Cells Expressing Human CD38 With or Without Its Cytoplasmic Domain J. Immunol., February 15, 1999; 162(4): 1952 - 1958. [Abstract] [Full Text] [PDF]

				L. Franco, L. Guida, S. Bruzzone, E. Zocchi, C. Usai, and A. D. Flora 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, November 1, 1998; 12(14): 1507 - 1520. [Abstract] [Full Text]

				H. Higashida, S. Yokoyama, M. Hashii, M. Taketo, M. Higashida, T. Takayasu, T. Ohshima, S. Takasawa, H. Okamoto, and M. Noda Muscarinic Receptor-mediated Dual Regulation of ADP-ribosyl Cyclase in NG108-15 Neuronal Cell Membranes J. Biol. Chem., December 12, 1997; 272(50): 31272 - 31277. [Abstract] [Full Text] [PDF]

				L. Franco, E. Zocchi, C. Usai, L. Guida, S. Bruzzone, A. Costa, and A. De Flora Paracrine Roles of NAD+ and Cyclic ADP-ribose in Increasing Intracellular Calcium and Enhancing Cell Proliferation of 3T3 Fibroblasts J. Biol. Chem., June 8, 2001; 276(24): 21642 - 21648. [Abstract] [Full Text] [PDF]