Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation

Peter W. Jurutka, J. C. Hsieh, Shigeo Nakajima, Carol A. Haussler, G. Kerr Whitfield, Mark R. Haussler

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

The potential functional significance of human 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor (hVDR) phosphorylation at Ser-208 was evaluated by cotransfecting COS-7 kidney cells with hVDR constructs and the catalytic subunit of human casein kinase II (CK-II). Under these conditions, hVDR is intensely phosphorylated in a reaction that depends on both CK-II and the presence of Ser-208. The resulting hyperphosphorylated receptor is unaltered in its kinetics for binding the 1,25(OH)2D3 ligand, its partitioning into the nucleus, and its ability to associate with a vitamin D responsive element. Replacement of Ser-208 with glycine or alanine indicates that phosphorylation of hVDR at Ser-208 is nut obligatory for 1,25(OH)2D3 action, but coexpression of wild-type hVDR and CK-II elicits a dose- dependent enhancement of 1,25(OH)2D3-stimulated transcription of a vitamin D responsive element reporter construct. This enhancement by CK-II is abolished by mutating Ser-208 to glycine or alanine and does not occur with glucocorticoid receptor-mediated transcription. Therefore, phosphorylation of hVDR by CK-II at Ser-208 specifically modulates its transcriptional capacity, suggesting that this covalent modification alters the conformation of VDR to potentiate its interaction with the machinery for DNA transcription.

Original languageEnglish (US)
Pages (from-to)3519-3524
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number8
DOIs
StatePublished - Apr 16 1996

Keywords

  • 1,25-dihydroxyvitamin D
  • control of transcription
  • rat osteocalcin gene
  • steroid, retinoid, and thyroid hormone receptors
  • vitamin D responsive element

ASJC Scopus subject areas

  • General

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