Effects of protein kinase A and calcium/phospholipid-dependent kinase modulators in the process of HL-60 cell differentiation: their opposite effects between HL-60 cell and K-562 cell differentiation.
We have previously shown that HL-60 cells treated with 1 alpha, 25-(OH)2D3 in magnesium-deficient medium are committed to differentiate but do not express differentiation-related phenotypes. In the present study, we demonstrated that Mg2+ deprivation blocked the process of differentiation before the induction of lysozyme mRNA and that the process of HL-60 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step. We studied the effects of protein kinase A (PKA) and calcium/phospholipid-dependent protein kinase (PKC) modulators at each step. The results indicated that agonists of PKA enhanced both steps but that N-(2-[methylamino]ethyl-5-isoquinolinesulfonamide inhibited them. On the other hand, 1-oleyl-2-acetylglycerol and 12-O-tetradecanoylphorbol-13-acetate enhanced the commitment step but inhibited that of phenotypic expression. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited the commitment step and enhanced that of phenotypic expression. These results indicate that PKA acts as a positive regulatory signal and that PKC has a dual role in the process of HL-60 cell differentiation, i.e., as a positive regulatory signal in the commitment step and as a negative one in the phenotypic expression step. Recently, we have also shown that in K-562 cell differentiation into erythroid lineage, PKA may serve as a negative regulatory signal in both steps; however, PKC may act dually, namely as a negative regulatory signal in the commitment step and as a positive one in the phenotypic expression step.(ABSTRACT TRUNCATED AT 250 WORDS)
Okuda
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Sawada
H
H
Kato
Y
Y
Yumoto
Y
Y
Ogawa
K
K
Tashima
M
M
Okuma
M
M
D000470:Alkaloids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute; D008274:Magnesium / Q000378:metabolism; D009113:Muramidase / Q000235:genetics; D010641:Phenotype; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D004075:Diglycerides; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D002762:Cholecalciferol; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; C038237:1-oleoyl-2-acetylglycerol; D011494:Protein Kinases; D011493:Protein Kinase C; D009113:Muramidase; D019311:Staurosporine; D008274:Magnesium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium