Activation of NF-kappa B mediates the PMA-induced differentiation of K562 cells

The role of NF-kappa B during the PMA-induced megakaryocytic differentiatio n of K562 cells was investigated using K562 cells transfected with each or both subunits of NF-kappa B. The NF-kappa B subunit-transfected cells have shown much higher sensitivity to PMA-induced differentiation than their par ental cells. This result was consistent with the findings that PMA-stimulat ed activities of NF-kappa B were markedly increased in the NF-kappa B subun it-transfected cells in comparison with their parental cells and PMA-induce d differentiation was enhanced by pretreatment with I kappa B-alpha: antise nse oligonucleotide in the NF-kappa B subunit-transfected cells. Meanwhile, there were basically no difference in the basal and PMA-stimulated MAP kin ase activities among the parental and NF-kappa B subunit-transfected cells, respectively. However, PMA-induced differentiation was blocked by pretreat ment with PD98059, a specific inhibitor of MEK, in both parental and NF-kap pa B-transfected cells. Therefore, these results suggest that during the PM A-induced megakaryocytic differentiation of K562 cells, NF-kappa B works do wnstream of MAP kinase, or that activation of both NF-kappa B and MAP kinas e pathways is involved. (C) 1998 Elsevier Science Ireland Ltd. All rights r eserved.