EPO-INDUCED HEMOGLOBINIZATION OF SKT6 CELLS IS MEDIATED BY MINIMAL CYTOPLASMIC DOMAINS OF THE EPO OR PROLACTIN RECEPTORS WITHOUT MODULATIONOF GATA-1 OR EKLF

Interaction of erythropoietin with its type 1 receptor is essential to the development of late erythroid progenitor cells, Through the ectop ic expression of receptor mutants in lymphoid and myeloid cell lines, insight has been gained regarding effectors that regulate Epo-induced proliferation, In contrast, effecters that regulate Epo-induced differ entiation events (e.g. globin gene expression) are largely undefined, For in vitro studies of this pathway, erythroleukemic SKT6 cell sublin es have been isolated which stably and efficiently hemoglobinize in re sponse to Epo, Epo rapidly activated Jak2, STAT5 and detectably STATs 1 and 3, while no effects on GATA-1, EKLF or STAT5 expression were obs erved, Finally, efficient hemoglobinization of SKT6 cells was shown to be mediated by chimeric receptors comprised of the EGF receptor extra cellular domain and truncated cytoplasmic subdomains of either the Epo receptor or the prolactin Nb2 receptor, This work further establishes SKT6 cells as an important model for studies of Epo-stimulated differ entiation, and shows that this signaling pathway is promoted by a limi ted set of membrane-proximal receptor domains and effectors.