Phosphorylation is involved in transcriptional activation by the 1,25-dihydroxyvitamin D3 receptor.
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.
Department of Biochemistry, University of Wisconsin-Madison, College of Agricultural and Life Sciences.
H M
HM
Darwish
J K
JK
Burmester
V E
VE
Moss
H F
HF
DeLuca
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019319:Okadaic Acid; D010766:Phosphorylation; D010957:Plasmids; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004988:Ethers, Cyclic; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002117:Calcitriol