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


CONCLUSIONS
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.
Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.
Christina J
CJ
Maier
Richard H
RH
Maier
Raphaela
R
Rid
Andrea
A
Trost
Harald
H
Hundsberger
Andreas
A
Eger
Helmut
H
Hintner
Johann W
JW
Bauer
Kamil
K
Onder
D002117:Calcitriol / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D020033:Protein Isoforms; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D004247:DNA; D051573:Proto-Oncogene Proteins c-pim-1; D002117:Calcitriol