Involvement of diverse protein kinase C isoforms in the differentiation of ML-1 human myeloblastic leukemia cells induced by the vitamin D3 analogue KH1060 and the phorbol ester TPA.
We reported previously that diverse combination of the vitamin D(3) analogue KH1060 together with 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically induces the differentiation of ML-1 cells into mature macrophages. To investigate the mechanism involved in their interaction, we examined the role of protein kinase C (PKC) in the differentiation of ML-1 cells to mature macrophages. We found that the specific PKC inhibitor GF109203 suppressed the morphological change and the alpha-naphthyl acetate esterase activity induced in ML-1 cells by treatment with KH1060 plus TPA. This treatment increased the translocation of PKC alpha, PKC epsilon, and PKC theta from cytosol to membranes. ML-1 cells treated with KH1060 alone increased translocation of PKC theta, whereas cells treated with TPA alone increased translocation of PKC alpha and PKC epsilon. These data showed that in human myeloblastic leukemia cells, diverse isoforms of PKC, including PKC alpha, epsilon, and theta, participate in the regulation of cell differentiation.
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12 Ichigaya, Funagawara-Machi, Shinjuku-ku, Tokyo 162-0826, Japan.
Takahisa
T
Shimizu
Nozomi
N
Taira
Mana
M
Senou
Ken
K
Takeda
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; C074279:KH 1060; C496628:PRKCA protein, human; C497255:PRKCE protein, human; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D020928:Mitogen-Activated Protein Kinases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate