PMID- 15474498
OWN - NLM
STAT- MEDLINE
DCOM- 20041220
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 324
IP  - 2
DP  - 2004 Nov 12
TI  - Phosphorylation of human vitamin D receptor serine-182 by PKA suppresses 
      1,25(OH)2D3-dependent transactivation.
PG  - 801-9
AB  - The human vitamin D receptor (hVDR), which is a substrate for several protein 
      kinases, mediates the actions of its 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 
      ligand to regulate gene expression. To determine the site, and functional impact, 
      of cAMP-dependent protein kinase (PKA)-catalyzed phosphorylation of hVDR, we 
      generated a series of C-terminally truncated and point mutant receptors. 
      Incubation of mutant hVDRs with PKA and [gamma-32P]ATP, in vitro, or 
      overexpressing them in COS-7 kidney cells labeled with [32P]orthophosphate, 
      revealed that serine-182 is the predominant residue in hVDR phosphorylated by 
      PKA. An aspartate substituted mutant (S182D), incorporating a negative charge to 
      mimic phosphorylation, displayed only 50% of the transactivation capacity in 
      response to 1,25(OH)2D3 of either wild-type or an S182A-altered hVDR. When the 
      catalytic subunit of PKA was overexpressed, a similar reduction in wild-type but 
      not S182D hVDR transactivity was observed. In a mammalian two-hybrid system, 
      S182D bound less avidly than wild-type or S182A hVDR to the retinoid X receptor 
      (RXR) heterodimeric partner that co-mediates vitamin D responsive element 
      recognition and transactivation. These data suggest that hVDR serine-182 is a 
      primary site for PKA phosphorylation, an event that leads to an attenuation of 
      both RXR heterodimerization and resultant transactivation of 1,25(OH)2D3 target 
      genes.
FAU - Hsieh, Jui-Cheng
AU  - Hsieh JC
AD  - Department of Biochemistry and Molecular Biophysics, College of Medicine, 
      University of Arizona, Tucson, AZ 85724, USA.
FAU - Dang, Hope T L
AU  - Dang HT
FAU - Galligan, Michael A
AU  - Galligan MA
FAU - Whitfield, G Kerr
AU  - Whitfield GK
FAU - Haussler, Carol A
AU  - Haussler CA
FAU - Jurutka, Peter W
AU  - Jurutka PW
FAU - Haussler, Mark R
AU  - Haussler MR
LA  - eng
GR  - DK-33351/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (DNA, Complementary)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Retinoid X Receptors)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Calcium/metabolism
MH  - Catalysis
MH  - Cyclic AMP-Dependent Protein Kinases/*chemistry/metabolism
MH  - DNA, Complementary/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Ligands
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Phosphorylation
MH  - Plasmids/metabolism
MH  - Receptors, Calcitriol/*chemistry
MH  - Retinoid X Receptors/metabolism
MH  - Serine/*chemistry
MH  - Transcriptional Activation
MH  - Transfection
MH  - Two-Hybrid System Techniques
EDAT- 2004/10/12 09:00
MHDA- 2004/12/21 09:00
CRDT- 2004/10/12 09:00
PHST- 2004/09/16 00:00 [received]
PHST- 2004/10/12 09:00 [pubmed]
PHST- 2004/12/21 09:00 [medline]
PHST- 2004/10/12 09:00 [entrez]
AID - S0006-291X(04)02186-2 [pii]
AID - 10.1016/j.bbrc.2004.09.139 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 Nov 12;324(2):801-9. doi: 
      10.1016/j.bbrc.2004.09.139.