|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1991 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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.