Physiological functions of the cell surface antigen CD38

细胞表面抗原CD38的生理功能

基本信息

批准号：
09044268
负责人：
KATADA Toshiaki
金额：
$ 4.35万
依托单位：
The University of Tokyo (Graduate School of Pharmaceutical Sciences)
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044268/
关键词：
cyclin ADP-ribose CD38 ecto-enzyme NADase retinoic acid signal transduction リンパ球細胞内陥入

项目摘要

Ecto-form NADase activity induced by retinoic acid (RA) in HL-60 cells is due to CD38, which has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase. CD38 catalyzes not only the hydrolysis of NAD^+, but also the formation and hydrolysis of cyclic ADP-ribose (cADPR), that is a novel mediator or modulator of Ca^<2+> release from intracellular Ca^<2+> stores. In the present study, we investigated the functions and properties of CD38 and obtained the following findings. 1. Stimulation of RA-differentiated HL-60 cells with anti-CD38 monoclonal antibodies induced rapid tyrosine phosphorylation of cellular proteins including the c-cbl proto-oncogene product, p12O^<c-Cbl>. Superoxide formation in response to formyl-Met-Leu-Phe was markedly enhanced by the anti-CD38 mAbs. Fcgamma-II receptors appeared to be involved in the signal transduction pathway mediated through the antiCD38 mAb-induced tyrosine phosphorylation. 2. CD38 was abundantly present in rat brain in addition to lymphocytes. In primary culture of rat glial and neuronal cells, CD38 was most abundantly observed in astrocyte cell surface. Confocal laser microscopic analysis revealed that immunoreactive CD38 and the enzyme activity were localized on the cell surface of astrocytes. The cell-surface CD38 was rapidly inactivated upon the addition of the enzyme substrates to the cultured astrocytes. 3. An RA response element (RARE) consisting of two directrepeated TGACCT-like hexamer motifs with a 5-nucleotide spacer was found to be located in the first intron of CD38 gene. This RARE interacted with heterodimer composed of RA receptor and retinoid X receptor. Thus, the RA-induced expression of human CD38 gene was demonstrated to be mediated through the RARE located in the first intron.

HL-60细胞中视黄酸（RA）诱导的eTo-form-NADase活性是由于CD38引起的，CD38具有与Aplysia adp-ribosyl Cyclase同源的氨基酸序列。 CD38不仅催化了NAD^+的水解，还催化了环状ADP-核糖（CADPR）的形成和水解，这是Ca^<2+>释放的新型介体或调节剂，从细胞内Ca^<2+> STORES释放。在本研究中，我们研究了CD38的功能和特性，并获得了以下发现。 1。用抗CD38单克隆抗体刺激RA分化的HL-60细胞诱导细胞蛋白的快速酪氨酸磷酸化，包括C-CBBL原始癌基因P12O^<c-CBL>。抗CD38 mAb明显增强了对甲基 - 米尔 - phe的响应的超氧化物形成。 FCGAMMA-II受体似乎参与了通过抗D38 mAb诱导的酪氨酸磷酸化介导的信号转导途径。除淋巴细胞外，大鼠脑中有大量CD38。在大鼠神经胶质细胞和神经元细胞的原发性培养中，在星形胶质细胞表面最多观察到CD38。共聚焦激光显微镜分析表明，免疫反应性CD38和酶活性位于星形胶质细胞的细胞表面。将酶底物添加到培养的星形胶质细胞中后，将细胞表面CD38迅速灭活。 3。由两个直接取代的TGACCT样己酰基基序和5-核苷酸间隔物组成的RA响应元件（稀有）位于CD38基因的第一个内含子中。这种稀有的与由RA受体和类维生素X受体组成的异二聚体相互作用。因此，证明了RA诱导的人CD38基因的表达是通过位于第一个内含子中的稀有子来介导的。