Evidence of the role of protein kinase C during aclacinomycin induction of erythroid differentiation in K562 cells.
At subtoxic concentrations, aclacinomycin is effective in controlling erythroid differentiation of K562, a human erythroleukemic cell line. To better understand early events implicated in this process, we have used bisindolylmaleimide (GF109203X), an inhibitor with a high selectivity for protein kinase C (PKC). Our data show that GF109203X inhibits aclacinomycin effects on K562, evidenced by a strong reduction of hemoglobinized cells and a marked decrease of mRNA rates of erythroid genes. To establish firmly PKC involvement, we also verified that aclacinomycin stimulates its rapid translocation, from the cytosolic to the membrane compartment. By Western blot analysis, we also show that after short induction times, PKCalpha was the most implicated.
Gillet
R
R
Laboratoire de Biochimie et Biologie Moléculaire, EA 2063, IFR 53, UFR Pharmacie, Reims, France.
Devemy
E
E
Dupont
C
C
Billat
C
C
Jeannesson
P
P
Trentesaux
C
C
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004900:Erythroblasts / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020014:K562 Cells; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C011157:aclacinomycins; D015250:Aclarubicin; D011493:Protein Kinase C; C070515:bisindolylmaleimide I