title: 1,25-Dihydroxyvitamin D3 induced activation and subsequent nuclear translocation of MAPK is upstream regulated by PKC in HL-60 cells.
abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) in addition to its classical role in calcium homeostasis regulates cell differentiation. The mechanisms involved in mediating numerous functions of 1,25(OH)2D3 are not clearly understood. In addition to genomic actions involving nuclear vitamin D receptor (VDR), some rapid nongenomic responses have been observed, but the full signalling pathway activated by 1,25(OH)2D3 has still not been described. Our recent data allow for better understanding of nongenomic effects evoked by 1,25(OH)2D3. In this paper we show that mitogen activated protein kinase (MAPK) is activated in HL-60 promyelocytic leukemia cells and in normal human keratinocytes under exposure to differentiation inducing concentrations of 1,25(OH)2D3. The MAPK is then transported to the cell nucleus in active form, which is different from the activation evoked by fetal calf serum. Experiments utilising tyrosine kinase inhibitor suggested that the postulated putative membrane vitamin D receptor, if it exists, does not have tyrosine kinase activity. Usage of protein kinase C (PKC) inhibitor allowed to state that PKC is an upstream element in the MAPK signalling pathway.
authors.affiliation: Department of Tumor Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. marcinko@immuno.pan.wroc.pl
authors.forename: E
authors.initials: E
authors.lastname: Marcinkowska
authors.forename: A
authors.initials: A
authors.lastname: Wiedłocha
authors.forename: C
authors.initials: C
authors.lastname: Radzikowski
mesh_terms: D001692:Biological Transport; D002117:Calcitriol / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D002451:Cell Compartmentation; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000201:enzymology; D003470:Culture Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003470:Culture Media; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002117:Calcitriol