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

A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis

“…K562 cells can undergo further differentiation in both megakaryocytic and erythroid lineages depending on the stimulus. Phorbol esters such as PMA-stimulated megakaryocytic differentiation (Shelly et al, 1998;Kim et al, 2001;Dorsey et al, 2002;Pettiford and Herbst, 2003), whereas hemin, hydroxyurea, Ara-C or as reported more recently imatinib mesylate (gleevec) induced erythroid differentiation of this cell line (Belhacene et al, 1998;Park et al, 2001;Jacquel et al, 2003;Kawano et al, 2004a, b). Megakaryocytic differentiation of K562 cells induced by PMA mimics, in part, the physiologic process that takes place in the bone marrow in response to a variety of stimuli (Long et al, 1990).…”

“…Megakaryocytic differentiation of K562 cells by PMA was only partly dependent on ERK/MAPK activity since it was significantly but not fully blocked by Uo126 and PD98059, two inhibitors of MEK1 (not shown). Accordingly, Shelly et al (1998) reported that PMA triggered phenotypic changes in K562 cells by both MAPK-dependent and -independent events. In agreement with the involvement of other signaling pathways, we established that complete differentiation (i.e.…”

The protein tyrosine phosphatase HePTP regulates nuclear translocation of ERK2 and can modulate megakaryocytic differentiation of K562 cells

“…Recent reports demonstrate that modulation of ERK and p38 activity is also involved in erythroid differentiation. Shelly et al 8 showed that the inhibition of basal ERK activity promoted erythroid differentiation. Similarly, Uchida et al 30 reported that inhibition of ERK1/2 promoted EPO-induced erythroid differentiation and inhibited TPO-induced megakaryocytic differentiation.…”

“…Erythroid differentiation is also associated with changes in MAP-kinase signaling. 8,9 Therefore we asked whether modulation of HePTP expression would have any effect on the erythroid differentiation of K562 cells. For this purpose, we treated our various K562 cell lines with the kinase inhibitor Herbimycin A which induces erythroid differentiation (Ref.…”

“…6,7 In these cells a low constitutive level of ERK activity is required for proliferation and treatment of the cells with the MEK inhibitor PD098059 results in downregulation of ERK activity and upregulation of erythroid markers. 8,9 Treatment of K562 cells with PMA, an activator of PKC, or expression of an activated MEK kinase induces prolonged ERK activity and megakaryocytic differentiation. 6,7 This differentiation process is characterized by cell cycle arrest, a change in the adhesive properties of the cells, and changes in cell morphology.…”