Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators

Gloria Arriagada, Roberto Paredes, Juan Olate, Andre J van Wijnen, Jane B. Lian, Gary S. Stein, Janet L. Stein, Sergio Onate, Martin Montecino

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Upon ligand binding the 1α,25-dihydroxy Vitamin D3 receptor (VDR) undergoes a conformational change that allows interaction with coactivator proteins including p160/SRC family members and the multimeric DRIP complex through the DRIP205 subunit. Casein kinase II (CKII) phosphorylates VDR both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of VDR to bind DNA, but increases its ability to transactivate target promoters. Here, we have analyzed whether phosphorylation of VDR by CKII modulates the ability of VDR to interact with coactivators in vitro. We find that both mutation of serine 208 to aspartic acid (VDRS208D) or phosphorylation of VDR by CKII enhance the interaction of VDR with DRIP205 in the presence of 1α,25-dihydroxy Vitamin D3. We also find that the mutation VDRS208D neither affects the ability of this protein to bind DNA nor to interact with SRC-1 and RXRα. Together, our results indicate that phosphorylation of VDR at serine 208 contributes to modulate the affinity of VDR for the DRIP complex and therefore may have a role in vivo regulating VDR-mediated transcriptional enhancement.

Original languageEnglish (US)
Pages (from-to)425-429
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Calcitriol Receptors
Phosphorylation
Serine
Aptitude
Casein Kinase II
Mediator Complex Subunit 1
dihydroxy-vitamin D3
Mutation
DNA
Hinges
Aspartic Acid
Proteins
Ligands

Keywords

  • 1α,25-Dihydroxy Vitamin D3 receptor
  • Coactivators
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators. / Arriagada, Gloria; Paredes, Roberto; Olate, Juan; van Wijnen, Andre J; Lian, Jane B.; Stein, Gary S.; Stein, Janet L.; Onate, Sergio; Montecino, Martin.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 103, No. 3-5, 03.2007, p. 425-429.

Research output: Contribution to journalArticle

Arriagada, Gloria ; Paredes, Roberto ; Olate, Juan ; van Wijnen, Andre J ; Lian, Jane B. ; Stein, Gary S. ; Stein, Janet L. ; Onate, Sergio ; Montecino, Martin. / Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators. In: Journal of Steroid Biochemistry and Molecular Biology. 2007 ; Vol. 103, No. 3-5. pp. 425-429.
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