PHOSPHORYLATION IS INVOLVED IN TRANSCRIPTIONAL ACTIVATION BY THE 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR

被引:39
作者
DARWISH, HM [1 ]
BURMESTER, JK [1 ]
MOSS, VE [1 ]
DELUCA, HF [1 ]
机构
[1] UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BIOCHEM,420 HENRY MALL,MADISON,WI 53706
关键词
VITAMIN-D; CALCIUM; BONE CALCIFICATION; STEROID; RECEPTOR;
D O I
10.1016/0005-2760(93)90213-S
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The 1,25-dihydroxyvitamin D3 receptor becomes phosphorylated upon treatment with 1,25-dihydroxyvitamin D3. We have investigated the role of phosphorylation in the transcriptional activity induced by 1,25-dihydroxyvitamin D3 through its receptor. An active 1,25-dihydroxyvitamin D3-dependent transcription system was reconstituted in CV-1 cells by co-transfection of plasmids containing the rat 1,25-(OH)2D3 receptor DNA and a functional vitamin D response element (DRE) in a reporter gene construct. Treatment of these transiently transfected CV-1 cells with modulators of protein kinase A (8-Br-cAMP, PKIA and H-9) and phosphatases (Okadaic acid) resulted in mimicking or abolishing the transcriptional activity of 1,25-dihydroxyvitamin D3 in a receptor-dependent fashion. These modulators directly altered 1,25-dihydroxyvitamin D3 receptor phosphorylation. Therefore, the present results strongly suggest that phosphorylation plays a central role in the transcriptional activity of the 1,25-dihydroxyvitamin D3 receptor.
引用
收藏
页码:29 / 36
页数:8
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