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

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

Research output: Contribution to journalArticle

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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

Fingerprint

Casein Kinase II
Calcitriol Receptors
Transcriptional Activation
Phosphorylation
Vitamin D
Alanine
Glycine
Nuts
Calcitriol
COS Cells
Glucocorticoid Receptors
Catalytic Domain
Ligands
Kidney
DNA

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

  • Genetics
  • General

Cite this

Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation. / Jurutka, Peter; Hsieh, J. C.; Nakajima, Shigeo; Haussler, Carol A.; Whitfield, G. Kerr; Haussler, Mark R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 8, 16.04.1996, p. 3519-3524.

Research output: Contribution to journalArticle

Jurutka, Peter ; Hsieh, J. C. ; Nakajima, Shigeo ; Haussler, Carol A. ; Whitfield, G. Kerr ; Haussler, Mark R. / Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 8. pp. 3519-3524.
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