Phosphorylation of the 1,25-dihydroxyvitamin D3 receptor. A primary event in 1,25-dihydroxyvitamin D3 action.

1,25-Dihydroxyvitamin D3 is believed to mediate the regulation of calcium metabolism by a steroid hormone receptor mechanism. We now demonstrate that phosphorylation of the 1,25-dihydroxyvitamin D3 receptor occurs rapidly in embryonic chick duodenal organ culture in response to 1,25-dihydroxyvitamin D3. Phosphorylation of the receptor is strongly induced within 1 h by 1,25-dihydroxyvitamin D3 and occurs prior to the initiation of calcium uptake or induction of calcium-binding protein in this system. Phosphorylation is not affected by inhibition of protein synthesis by cycloheximide. Since chick duodenal organ culture is a vitamin D-responsive system that closely parallels in vivo rachitic chicken intestine, the occurrence of receptor phosphorylation in response to 1,25-dihydroxyvitamin D3 strongly suggests that it is a physiologically relevant event. In addition, since it occurs prior to the other responses to 1,25-dihydroxyvitamin D3, it appears possible that phosphorylation may play a significant role in the 1,25-dihydroxyvitamin D3 regulation of transcription in the intestine.