Requirement of thrombopoietin-induced activation of ERK for megakaryocyte differentiation and of p38 for erythroid differentiation

Abstract

Thrombopoietin (TPO) plays a critical role not only in proliferation and differentiation of megakaryocytes but also in erythroid differentiation. We have investigated whether the different pathway of mitogen-activated protein kinase (MAPK) after TPO stimulation may discriminate megakaryocyte and erythroid differentiation. In this study, we have used human CD34+ hematopoietic progenitor cells (HPCs) from cord blood (CB) in serum-free liquid culture supplemented with TPO, to compare the respective effects of specific inhibitors of MAPK kinase (MEK) (PD98059) and p38 MAP kinase (p38) (SB203580) on megakaryocyte and erythroid development. PD98059, but not SB203580, significantly suppressed TPO-induced megakaryocyte differentiation when examined by the expression of CD41 and polyploidy assay. In the presence of SB203580, CD34+/CD36+ erythroid progenitors clearly decreased, whereas they increased when cultured with PD98059. These results indicate that activation of extracellular-signal-regulated kinase (ERK) is required for TPO-induced megakaryocyte differentiation and that p38 is required for TPO-induced erythroid differentiation.

ERK2-Pyruvate Kinase Axis Permits Phorbol 12-Myristate 13-Acetate-induced Megakaryocyte Differentiation in K562 Cells

“…However, ERK activation was observed essential for nuclear translocation of PKM2, and not PKR isoform, substantiating the likelihood of a crucial role of nuclear PKM2 in differentiation, which is yet to be explored. PMA induced a p38 pathway, but inhibition of this pathway did not affect the PMA-induced megakaryocyte differentiation in K562 cells, consistent with other reports (50,51).…”

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

“…Consistent with this, other reports suggest that ERK activation is required for megakaryocytic differentiation and that erythroid differentiation requires p38 activation. 31,32 Here, it should be noted that we have not observed an effect of HePTP overexpression or HePTP inhibition on the basal activity of ERK in K562 cells (see Figure 1b). In contrast to the above mentioned reports, Woessman and Mivechi 33 found that a dominant negative ERK1 blocked hemin-induced erythroid differentiation of K562 cells.…”

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

“…99 p38 MAPK is activated in established megakaryocytic cell lines and is involved in erythroid differentiation. 100 Here, the tested MAPKs, namely JNK and p38, were upregulated in the F9 cells treated with RA, as well as in cells treated with low and high concentration of AgNPs, whereas the cells treated in the presence of cisplatin showed diminished expression levels of both JNK and p38. Altogether, these findings suggest that cisplatin inhibits AgNPsinduced expression of Gata6, Wnt-5, β-catenin, GSK-3, Rho, JNK, and p-p38 and eventually induces differentiation process.…”