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. © 2012 Maier et al.; licensee BioMed Central Ltd.
Maier, C. J., Maier, R. H., Rid, R., Trost, A., Hundsberger, H., Eger, A., … Onder, K. (2012). PIM-1 kinase interacts with the DNA binding domain of the vitamin D receptor: A further kinase implicated in 1,25-(OH) 2D 3 signaling. BMC Molecular Biology, 13. https://doi.org/10.1186/1471-2199-13-18