Up‐regulation of protein serine/threonine phosphatase type 2C during 1α,25‐dihydroxyvitamin D3‐induced monocytic differentiation of leukemic HL‐60 cells

摘要

>Treatment with 20 nM 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) caused a progressive increase in the activity of Mg2+-dependent protein serine/threonine phosphatase type 2C (PP2C) in subcellular fractions of HL-60 cells, whereas PP2C activity was relatively constant throughout all-trans retinoic acid-induced (1 μM) granulocytic differentiation. The increase in PP2C activity appeared to parallel the 1,25(OH)₂D₃-induced phenotypic and functional changes in HL-60 cells. Immunoblot and Northern blot analysis indicated that the increase in PP2C activity corresponded to the increased expression of PP2C protein, which was preceded by an increase in the level of mRNA for PP2Cβ. No mRNA for PP2Cα was detected in resting or 1,25(OH)₂D₃-stimulated HL-60 cells. These results suggest that the increased expression of PP2C is related with the 1,25(OH)₂D₃-induced monocytic differentiation of HL-60 cells.