Involvement of phosphatidylinositol 3-kinase in the mediation of erythropoietin-induced activation of p70(S6k)

We have previously shown that, in HCD-57 cells, erythropoietin (EPO) induces a biphasic activation of the ribosomal S6 kinase p70(S6k), an enzyme playing a key role in the regulation of cell cycle progression. Here we present evidence that p70(S6k) is activated through both phosphatidylinositol (PI) 3-kinase-dependent and -independent pathways: whereas the early phase of EPO dependent stimulation of p70(S6k) activity was strongly suppressed by the potent PI 3-kinase inhibitor wortmannin, late phase was much less affected. The dose-dependent inhibition of cell growth by wortmannin indicates an important role of PI 3-kinase in the mediation of EPO induced cell proliferation. Furthermore, our data suggest that the EPO-receptor associated tyrosine kinase JAK2 is not essentially involved in the mediation of EPO-induced p70(S6k) activation. (C) 1997 Elsevier Science Inc.