Effects of protein kinase modulators on transferrin receptor expression in human leukaemic HL-60 cells.
The mRNA of transferrin receptor (TfR) is constitutively expressed in proliferating human leukaemic HL-60 cells. Treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, or dibutyryl-cyclic AMP (dbcAMP), a protein kinase A (PKA) activator, resulted in a 90% decrease in the level of TfR mRNA. Inhibition of TfR mRNA expression induced by 10 nM PMA and 100 microM dbcAMP was abolished by prior incubation of cells with 0.1-1.0 microM GF109203X, a PKC-specific inhibitor, and 1-10 microM H-89, a PKA-specific inhibitor, respectively. The blocking effects of GF109203X and H-89 were dose-dependent and complete at the highest concentrations of the inhibitors used. Although treatment of cells with GF109203X or H-89 alone did not alter the constitutive expression of TfR mRNA, incubation of cells with 30-100 nM staurosporine, a wide-spectrum protein kinase inhibitor, resulted in suppression of the constitutive expression of TfR mRNA in a dose-dependent manner. These results suggest that (i) the down-regulation of TfR mRNA expression during the differentiation of HL-60 cells can be mediated by activation of either PKC or PKA; (ii) the constitutive expression of TfR mRNA in proliferating HL-60 cells is staurosporine-sensitive and is probably maintained by protein kinase(s) other than PKC and PKA.
Lok
C N
CN
Department of Physiology, Faculty of Medicine, University of Hong Kong.
Chan
K F
KF
Loh
T T
TT
D000470:Alkaloids / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis*; D019311:Staurosporine; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D004273:DNA, Neoplasm; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D013449:Sulfonamides; D003994:Bucladesine; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine