Source:http://linkedlifedata.com/resource/pubmed/id/17327484
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
2007-5-3
|
pubmed:databankReference | |
pubmed:abstractText |
1,25-dihydroxycholecalciferol, also known as 1alpha,25-dihydroxyvitamin D3 or calcitriol, regulates the differentiation and functional properties of mononuclear phagocytes. Many of these effects involve nongenomic signaling pathways, which are not fully understood. Activation of CD14 expression, a monocyte differentiation marker and coreceptor with TLR-2 for bacterial LPS, by calcitriol was shown previously to be PI-3K-dependent [1]; however, the mechanism of gene activation remained undefined. Using a transcription factor-binding array screen coupled with EMSA, we found evidence for PI-3K-dependent activation of CREB in THP-1 cells incubated with calcitriol. Furthermore, analysis of the proximal promoter of human CD14 identified regions that contained up to seven sequences, which showed significant similarity to a canonical CRE sequence, 5'-TGACGTCA-3'. Treatment of THP-1 cells with calcitriol activated CREB binding to one of these regions at Positions -37 to -55, relative to the transcription start site in a PI-3K-dependent manner. This 19-mer region also became transcriptionally active in a reporter assay in response to calcitriol, again dependent on PI-3K. Mutation of the CRE within the 19-mer abolished this activity. Taken together, these results show that calcitriol signaling, leading to activation of the CD14 promoter, involves CREB activation downstream of PI-3K.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0741-5400
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
81
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1311-21
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:17327484-Antigens, CD14,
pubmed-meshheading:17327484-Base Sequence,
pubmed-meshheading:17327484-Binding Sites,
pubmed-meshheading:17327484-Calcitriol,
pubmed-meshheading:17327484-Cell Line,
pubmed-meshheading:17327484-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:17327484-HeLa Cells,
pubmed-meshheading:17327484-Humans,
pubmed-meshheading:17327484-Molecular Sequence Data,
pubmed-meshheading:17327484-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17327484-Promoter Regions, Genetic,
pubmed-meshheading:17327484-Protein Binding,
pubmed-meshheading:17327484-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17327484-Structure-Activity Relationship
|
pubmed:year |
2007
|
pubmed:articleTitle |
1alpha,25-dihydroxycholecalciferol activates binding of CREB to a CRE site in the CD14 promoter and drives promoter activity in a phosphatidylinositol-3 kinase-dependent manner.
|
pubmed:affiliation |
Department of Medicine, University of British Columbia, Rm. 452D, 2733 Heather St., Vancouver, BC, Canada, V5Z 3J5.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|