ERK/MAPK pathway is required for changes of cyclin D1 and B1 during phorbol 12-myristate 13-acetate-induced differentiation of K562 cells.
Phorbol 12-myristate 13-acetate (PMA)-induced differentiation of human erythroleukemic K562 cells is characterized by growth arrest, morphological change, and expression of megakaryocyte-specific proteins. We examined the possible involvement of cell cycle regulators with PMA-induced growth arrest and megakaryocytic differentiation of K562 cells. The concentrations of cyclin D1 and p21Waf1/Cip1 were dramatically increased, whereas those of cyclin B1 and cdc2 were decreased, by PMA treatment. The concentrations of most cyclin-dependent kinases (Cdk2, Cdk4, and Cdk6), however, were unchanged by PMA treatment. PD98059, a specific inhibitor of MEK1, partially prevented the increase in cyclin D1 caused by PMA and fully reversed the down-regulation of cyclin B1 protein seen in response to PMA treatment. Thus, it is demonstrated here that the PMA-mediated changes of cyclin D1 and B1 are the result of a persistent increase in extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) activity.
Lee
C H
CH
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Korea.
Yun
H J
HJ
Kang
H S
HS
Kim
H D
HD
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D019938:Cyclin D1 / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D019938:Cyclin D1; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate