ERYTHROPOIETIN STIMULATES GLYCOSYLPHOSPHATIDYLINOSITOL HYDROLYSIS IN RAT ERYTHROID PROGENITOR CELLS AND INOSITOLPHOSPHATE GLYCAN MODULATES THEIR PROLIFERATION

The involvement of a glycosylphosphatidylinositol/inositolphosphate glycan (GPI/IPG) system in the erythropoietin (Epo) signal transduction was investigated. Endogenous GPI was evidenced in extracts of normal Epo-responsive cells after incorporation of [H-3]glucosamine, [H-3]inositol and [P-32]orthophosphate. Incubation of these cells with Epo produced a rapid and transient hydrolysis of GPI with parallel release of IPG. IPG production was Epo dose dependent and the maximal effect was obtained with the same concentration of Epo which gave the maximal mitogenic effect, i.e. 1 U/ml. The number and size of erythroid colonies (CFU-E) were increased by the addition of purified rat erythroid IPG to the culture medium, but not to the same extent as with a maximal Epo treatment. Exogenous IPG effect was dose dependent. In the presence of suboptimal Epo concentrations, IPG has been found to potentiate Epo-induced CFU-E growth. These results support the hypothesis that a GPI/IPG based signal transduction system may be involved in Epo-induced cell proliferation.