Sustained Activation of the Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway Is Required for Megakaryocytic Differentiation of K562 Cells

PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events

“…63,66 More recently, several reports have demonstrated that the MEK/MAPK pathway plays a crucial role in the modulation of megakaryocyte differentiation downstream from PKC activation. [23][24][25]27 The results described above, taken together with a previously published work, 25 support the suggestion that the MEK/MAPK pathway plays a switch role in determining the lineage commitment of K562 cells. The exact molecular steps involved in this process are unknown but undoubtedly involve changes in gene expression 1,2 that either positively or negatively modulate erythroid differentiation.…”

“…Thus, polylobulation of the nucleus is not sufficient nor is it required for the expression of CD41, a marker for megakaryocyte differentiation whose expression is dependent on a functional MEK/MAPK pathway. 23,25,27 A recent study suggests that polyploidy and functional maturation during megakaryocyte differentiation are two distinct events. 56 The above described results illustrate that specific changes associated with PMA treatment of K562 cells are either dependent, thus differentiation linked, or independent of the MEK/MAPK pathway.…”

“…8 Both the growth inhibitory effect and megakaryocytic differentiation of K562 cells seen with PMA are mediated by prolonged activation of the MAPK pathway. 23,25,27 We wanted to determine whether prolonged activation of MAPK was due to continuous activation of two of its upstream regulators, MEK1 and MEK2, or to modulation of a downstream inactivator such as dual specificity phosphatases. Thus, we preactivated MAPK by incubation of K562 cells with PMA in the absence of the MEK inhibitor, PD098059 37,38 and followed the rate of disappearance of dual phosphorylated MAPK upon addition of the MEK inhibitor.…”

“…8 More recently, several reports have demonstrated that the MEK/MAPK pathway plays a crucial role in the modulation of megakaryocyte differentiation downstream from PKC activation. [23][24][25][26][27] Erythroid differentiation of K562 cells is less well characterized. In vitro, differentiation of K562 cells toward the erythroid lineage can be modulated by an array of agents and/or manipulations.…”

MAPK‐dependent expression of p21WAF and p27kip1 in PMA‐induced differentiation of HL60 cells

“…Although a role of the ERK pathway in growth arrest or cellular di¡erentiation is not unprecedented [3,11,12], our results are the ¢rst of its kind that establish a link between ERK activation and p21 WAF and p27 kip1 induction in the process of cellular di¡erentiation. The mechanism by which PMA-induced activation of ERK leads to induction of p21 WAF and p27 kip1 and terminal di¡erentiation in HL60 cells is not clear.…”