

Author: Marcinkowska E. Więdłocha A. Radzikowski C.
Publisher: Elsevier
ISSN: 0006-291X
Source: Biochemical and Biophysical Research Communications, Vol.241, Iss.2, 1997-12, pp. : 419-426
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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)2D3are 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)2D3has 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.
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