GSBS Student Publications
Title
Phosphorylation at serine 208 of the 1alpha,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology
Date
3-21-2007
Document Type
Article
Medical Subject Headings
Mutation; Phosphoserine; Protein Binding; Receptors, Calcitriol; Trans-Activators
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Upon ligand binding the 1alpha,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 1alpha,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 RXRalpha. 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.
Rights and Permissions
Citation: J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):425-9. Link to article on publisher's site
DOI of Published Version
10.1016/j.jsbmb.2006.12.021
Related Resources
Journal Title
The Journal of steroid biochemistry and molecular biology
PubMed ID
17368182
Repository Citation
Arriagada, Gloria; Paredes, Roberto; Olate, Juan; Van Wijnen, Andre J.; Lian, Jane B.; Stein, Gary S.; Stein, Janet L.; Onate, Sergio; and Montecino, Martin A., "Phosphorylation at serine 208 of the 1alpha,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators" (2007). GSBS Student Publications. 54.
https://escholarship.umassmed.edu/gsbs_sp/54