First Author | Tohgo A | Year | 1994 |
Journal | J Biol Chem | Volume | 269 |
Issue | 46 | Pages | 28555-7 |
PubMed ID | 7961800 | Mgi Jnum | J:21495 |
Mgi Id | MGI:69457 | Doi | 10.1016/s0021-9258(19)61940-x |
Citation | Tohgo A, et al. (1994) Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38. J Biol Chem 269(46):28555-7 |
abstractText | We have recently demonstrated that cyclic ADP-ribose (cADPR) serves as a second messenger for glucose-induced insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373) and that human leukocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Although the amino acid sequence of Aplysia ADP-ribosyl cyclase exhibits a high degree of amino acid sequence identity with that of CD38, the Aplysia enzyme shows only ADP-ribosyl cyclase but not cADPR hydrolase. In the present study, we introduced site-directed mutations to CD38 and found that C119K- and/or C201E-CD38 exhibited only ADP-ribosyl cyclase activity. Furthermore, Aplysia ADP-ribosyl cyclase into which we introduced the mutations K95C and E176C, which correspond to residues 119 and 201 of human CD38, exhibited not only ADP-ribosyl cyclase activity but also cADPR hydrolase. These results indicate that cysteine residues 119 and 201 in CD38 have crucial roles in the synthesis and hydrolysis of cADPR. |