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Open Access Research article

PIM-1 kinase interacts with the DNA binding domain of the vitamin D receptor: a further kinase implicated in 1,25-(OH)2D3 signaling

Christina J Maier1, Richard H Maier1, Raphaela Rid1, Andrea Trost3, Harald Hundsberger2, Andreas Eger2, Helmut Hintner1, Johann W Bauer1 and Kamil Onder1*

Author affiliations

1 Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria

2 IMC Fachhochschule Krems, Krems, Austria

3 Department of Ophthalmology and Optometry, SALK/Paracelsus Medical University, Salzburg, Austria

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Citation and License

BMC Molecular Biology 2012, 13:18  doi:10.1186/1471-2199-13-18

Published: 21 June 2012

Abstract

Background

The vitamin D3 receptor (VDR) is responsible for mediating the pleiotropic and, in part, cell-type-specific effects of 1,25-dihydroxyvitamin D3 (calcitriol) on the cardiovascular and the muscle system, on the bone development and maintenance, mineral homeostasis, cell proliferation, cell differentiation, vitamin D metabolism, and immune response modulation.

Results

Based on data obtained from genome-wide yeast two-hybrid screenings, domain mapping studies, intracellular co-localization approaches as well as reporter transcription assay measurements, we show here that the C-terminus of human PIM-1 kinase isoform2 (amino acid residues 135–313), a serine/threonine kinase of the calcium/calmodulin-regulated kinase family, directly interacts with VDR through the receptor’s DNA-binding domain. We further demonstrate that PIM-1 modulates calcitriol signaling in HaCaT keratinocytes by enhancing both endogenous calcitriol response gene transcription (osteopontin) and an extrachromosomal DR3 reporter response.

Conclusion

These results, taken together with previous reports of involvement of kinase pathways in VDR transactivation, underscore the biological relevance of this novel protein-protein interaction.

Keywords:
Coactivator; PIM-1 kinase; Protein-Protein interaction; Serine/Threonine kinase; Vitamin D; Vitamin D receptor