Tyrosine residues of the erythropoietin receptor are dispensable for erythroid differentiation of human CD34+ progenitors

To study the role of the cytoplasmic domain and particularly the tyrosine r esidues of the erythropoietin receptor (EpoR) in erythroid differentiation of human primary stem cells, we infected cord blood-derived CD34+ cells wit h retroviruses encoding chimeric receptors containing the extracellular dom ain of the prolactin receptor (PRLR) and the cytoplasmic domain of either t he normal EpoR or a truncated EpoR devoid of tyrosine residues. Erythroid d ifferentiation of the infected progenitors could thus be studied after stim ulation by PRL. The complete PRLR was used to assess its ability to substit ute for EpoR in erythroid differentiation. Typical erythroid day-14 colonie s were observed from CD34+ cells grown in PRL when infected with any of the three viral constructs. These results demonstrate that: (i) the activation of the virally transduced PRLR leads to erythroid colony formation showing that erythroid terminal differentiation can be induced by a nonerythroid r eceptor in human progenitors; (ii) a chimeric receptor PRLR/EpoR is able to transduce a signal leading to terminal erythroid differentiation of human CD34+ cells; (iii) in contrast to results previously reported in murine mod els, tyrosine residues of the EpoR are not required for growth and terminal differentiation of human erythroid progenitors. (C) 1999 Academic Press.