Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.
BMC Mol Biol. 2012 Jun 21;13:18. doi: 10.1186/1471-2199-13-18.
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.
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.
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.
维生素 D3 受体（VDR）负责介导 1,25-二羟维生素 D3（骨化三醇）对心血管和肌肉系统、骨骼发育和维持、矿物质稳态、细胞增殖、细胞分化、维生素 D 代谢和免疫反应调节的多效性和部分细胞类型特异性作用。
基于从全基因组酵母双杂交筛选、结构域映射研究、细胞内共定位方法以及报告转录测定中获得的数据，我们在此表明人 PIM-1 激酶同工酶 2（氨基酸残基 135-313）的 C 端，钙/钙调蛋白调节激酶家族的丝氨酸/苏氨酸激酶，通过受体的 DNA 结合域直接与 VDR 相互作用。我们进一步证明 PIM-1 通过增强内源性骨化三醇反应基因转录（骨桥蛋白）和染色体外 DR3 报告基因反应来调节 HaCaT 角质形成细胞中的骨化三醇信号。
这些结果与激酶途径参与 VDR 反式激活的先前报道一起，强调了这种新的蛋白质-蛋白质相互作用的生物学相关性。
