PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events.
Erythroid and megakaryocyte lineages are closely linked and may share a common bipotent progenitor. However, the mechanisms associated with cell lineage commitment are not fully understood. The K562 erythroleukemia cell line serves as a model to study the biochemical changes associated with erythroid and megakaryocyte (E/M) differentiation. We have previously established that PMA-induced megakaryocyte differentiation of K562 cells requires the activity of the MEK/MAPK pathway (Herrera et al Exp Cell Res 1998; 238: 407-414). Here, we show that the PMA-induced phenotypic changes of K562 cells such as polylobulation of the nucleus and Pyk2 expression are independent of MAPK activation. In addition, we also demonstrate that inhibition of the basal activity of the extracellular regulated kinase (ERK/MAPK) pathway enhances the erythroid phenotype of these cells. These results suggest that the MAPK pathway regulates the E/M lineage commitment of K562 cells.
Shelly
C
C
Department of Cell Biology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Petruzzelli
L
L
Herrera
R
R
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051418:Focal Adhesion Kinase 2; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate