Activation of intracellular signaling pathways is necessary for an increase in VDR expression and its nuclear translocation.

1,25-Dihydroxyvitamin D(3) (1,25D) regulates gene transcription through the nuclear vitamin D receptor (VDR) and initiates rapid cellular responses via an unknown mechanism. Here we report that 1,25D induces a rapid increase in synthesis of VDR protein and its transport to the nucleus. These results are similarly obtained in myeloid leukemia cell lines, and in blast cells from blood of patients diagnosed with acute myeloid leukemia, subtypes M2 and M4. Our results suggest that stability of unliganded VDR is LY294002- and PD98059-dependent, and that ligation of VDR leads to its increased translation and nuclear translocation. The receptor localized in the cell nucleus is not exported back to the cytosol by exportin 1. We also show that the cytosolic portion of VDR in leukemia cells is localized in the vicinity of the plasma membrane, close to the F-actin cytoskeleton.