JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells

Jun N-terminal kinase (JNK) and p38, members of the mitogen-activated prote in kinase family of serine/threonine kinases, are activated as a result of cellular stress but may also play a role in growth factor-induced prolifera tion and/or survival or differentiation of many cells. A recent report has implicated JNK and p38 in the induction of apoptosis in the erythropoietin (EPO)-dependent erythroid cell line HCD57 following EPO withdrawal, whereas our previously reported data did not support a role for JNK in growth fact or withdrawal-induced apoptosis in HCD57 cells. Therefore, further testing was done to see if JNK was activated in EPO withdrawal-induced apoptosis; t he study was extended to p38 and characterized the effect of EPO on JNK and p38 activities, Treatment of HCD57 cells with EPO resulted in a gradual an d sustained activation of both JNK and p38 activity; these activities decre ased on EPO withdrawal, Transient activation of p42/p44 extracellular signa l-related kinases (ERK) was also detected. Inhibition of ERK activity inhib ited proliferation in EPO-treated cells but neither induced apoptosis nor a ctivated JNK, Inhibition of p38 activity inhibited proliferation but did no t protect HCD57 cells from apoptosis induced by EPO withdrawal, Treatment o f HCD57 cells with tumor necrosis factor-alpha induced JNK activation but d id not induce apoptosis. These results implicate JNK, p38, and ERK in EPO-i nduced proliferation and/or survival of erythroid cells but do not support a role for JNK or p38 in apoptosis induced by EPO withdrawal from erythroid cells, (C) 2000 by The American Society of Hematology.