1,25-DIHYDROXYVITAMIN D-3 INDUCED ACTIVATION AND SUBSEQUENT NUCLEAR TRANSLOCATION OF MAPK IS UPSTREAM REGULATED BY PKC IN HL-60 CELLS

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) in addition to its classica l role in calcium homeostasis regulates cell differentiation. The mech anisms involved in mediating numerous functions of 1,25(OH)(2)D-3 are not clearly understood. in addition to genomic actions involving nucle ar vitamin D receptor (VDR), some rapid nongenomic responses have been observed, but the full signalling pathway activated by 1,25(OH)(2)D-3 has still not been described. Our recent data allow for better unders tanding of nongenomic effects evoked by 1,25(OH)(2)D-3. In this paper we show that mitogen activated protein kinase (MAPK) is activated in H L-60 promyelocytic leukemia cells and in normal human keratinocytes un der exposure to differentiation inducing concentrations of 1,25(OH)(2) D-3. The MAPK is then transported to the cell nucleus in active form, which is different from the activation evoked by fetal calf serum. Exp eriments utilising tyrosine kinase inhibitor suggested that the postul ated putative membrane vitamin D receptor, if it exists, does not have tyrosine kinase activity. Usage of protein kinase C (PKC) inhibitor a llowed to state that PKC is an upstream element in the MAPK signalling pathway. (C) 1997 Academic Press.