| Project/Area Number |
06454651
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | The University of Tokyo (Faculty of Pharmaceutical Sciences) |
|---|
Principal Investigator |
KATADA Toshiaki The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Chem., Professor, 薬学部, 教授 (10088859)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HOSHINO Shin-ichi The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Che, 薬学部, 助手 (40219168)
HAZEKI Osamu The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Che, 薬学部, 講師 (80142751)
仁科 博史 東京工業大学, 生命理工学部, 助手 (60212122)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1994: ¥4,900,000 (Direct Cost: ¥4,900,000)
|
|---|
| Keywords | NAD / cyclic ADP-ribose / NAD-cleavage enzyme / ADP-ribosyl cyclase / CD38 / calcium ion / signal transduction |
|---|
| Research Abstract |
The human cell surface antigen CD38, which has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase, is a 46-kDa type II glycoprotein with a single-transmembrane domain. We previously demonstrated that the extracellular domain of CD38 exhibits NAD^+ glycohydrolase (NADase) activity and that the ecto-form NADase activity induced by all-trans retinoic acid (RA) in HL-60 cells is due to CD38 (Kontani, K.et al., J.Biol.Chem.268 : 16895,1993). CD38 catalyzes not only the hydrolysis of NAD^+, but also the formation and hydrolysis of cyclic ADP-ribose, which is a novel candidate that mediates Ca^<2+> release from intracellular Ca^<2+> stores. In the present study, we obtained the following findings. 1. Besides these enzyme activities, CD38 had the ability to bind hyaluronate. 2. Stimulation of RA-differentiated HL-60 cells with anti-CD38 monoclonal antibody (mAb) induced rapid tyrosine phosphorylation of cellular proteins with the molecular weight of 120,000,87,000 and 77,000. One of the prominent phosphorylated proteins was identified as the c-cbl proto-oncogene product, p120^<c-cbl>.3. Superoxide formation in response to formyl-Met-Leu-Phe was markedly enhanced by the anti-CD38 mAb in the differentiated HL-60 cells. 4. Zn^<2+> directly interacted with CD38 to convert its catalytic properties from NADase to ADP-ribosyl cyclase, probably due to prevention of the access of water molecule to an intermediate of the enzyme-substrate complex. 5. Although the expression of CD38 mRNA was mediated through nuclear RA receptors, a negative regulatory element present in the first intron of CD38 gene appeared to be involved in the RA-induced expression of CD38 mRNA in HL-60 cells.
|
