权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Significance of vitamin D receptor phosphorylation in an activation step of vitamin D transduction system

维生素 D 受体磷酸化在维生素 D 转导系统激活步骤中的意义

基本信息

批准号：
03671160
负责人：
INABA Masaaki
金额：
$ 1.34万
依托单位：
Osaka City University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Vitamin D receptor (VDR) belongs to steroid hormone receptor superfamily. VDR is activated to bind tightly to its vitamin D responsive element by binding to its active ligand, 1,25-dihydroxyvitamin D(1,25D). In this process, 1,25D is known to stimulate the phosphorylation of its cognate receptor, as in the other steroid hormones, such as glucocorticoid and progesterone. However, its physiological significance is yet to be known, in the beginning of this study. However, in the process of this study, other groups reported that both PKC and PKA can stimulate VDR phosphorylation. Because cross-talk between VDR and PKC or PKA system is known, I changed the focus of this study on from the significance of VDR phosphorylation to the modulatory effect of PKA or PKC activator on 1,25D action. In the two papers thanks to the support of this grant, I reported that PKA activators enhance the effect of 1,25D both by increasing VDR receptor and at its postreceptor steps and that intracellular cAMP concentration is one of major determinant for the magnitude of 1,25D action. Furthermore, a PKC activator, TPA, increases VDR receptor by the mechanism distinct from PKA system and enhances 1,25D effect. The study to determine the correlation between the magnitude of those reagents on VDR phosphorylation level and on their enhancement on 1,25D action is now under way.

维生素D受体（VDR）属于类固醇激素受体超家族。VDR通过与其活性配体1，25-二羟基维生素D（1，25 D）结合而被激活以紧密结合其维生素D响应元件。在这个过程中，已知1，25 D刺激其同源受体的磷酸化，如在其他类固醇激素中，如糖皮质激素和孕酮。然而，在本研究开始时，其生理学意义尚不清楚。然而，在本研究的过程中，其他研究小组报道PKC和PKA都可以刺激VDR磷酸化。由于VDR与PKC或PKA系统之间的相互作用是已知的，因此我将本研究的重点从VDR磷酸化的意义转移到PKA或PKC激活剂对1，25 D作用的调节作用。在这两篇论文中，感谢该基金的支持，我报道了PKA激活剂通过增加VDR受体及其受体后步骤增强1，25 D的作用，并且细胞内cAMP浓度是1，25 D作用大小的主要决定因素之一。此外，PKC激活剂TPA通过与PKA系统不同的机制增加VDR受体并增强1，25 D效应。目前正在进行研究，以确定这些试剂对VDR磷酸化水平的影响程度及其对1，25 D作用的增强作用之间的相关性。