The prolactin receptor rescues EpoR-/- erythroid progenitors and replaces EpoR in a synergistic interaction with c-kit

• Published in: Blood Vol. 92; no. 5; pp. 1491 - 1496
• Main Authors: SOCOLOVSKY, M, FALLON, A. E. J, LODISH, H. F
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01.09.1998
• Subjects: Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Drug Synergism; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - metabolism; Female; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular and cellular biology; Prolactin - pharmacology; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - physiology; Rabbits; Receptors, Erythropoietin - deficiency; Receptors, Erythropoietin - genetics; Receptors, Erythropoietin - physiology; Receptors, Prolactin - genetics; Receptors, Prolactin - physiology; Recombinant Fusion Proteins - physiology; Recombinant Proteins; Signal Transduction; Stem Cell Factor - pharmacology; Erythropoiesis; Human; Protein hormone; Adenohypophyseal hormone; Erythroid cell; Erythropoietin; Prolactin; Molecular interaction; Glycoprotein hormone; Cell differentiation; Biological receptor; Hormonal receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v92.5.1491

We recently showed that a retrovirally transduced prolactin receptor (PrlR) efficiently supports the differentiation of wild-type burst-forming unit erythroid (BFU-e) and colony-forming unit erythroid (CFU-e) progenitors in response to prolactin and in the absence of erythropoietin (Epo). To examine directly whether the Epo receptor (EpoR) expressed by wild-type erythroid progenitors was essential for their terminal differentiation, we infected EpoR-/- progenitors with retroviral constructs encoding either the PrlR or a chimeric receptor containing the extracellular domain of the PrlR and intracellular domain of EpoR. In response to prolactin, both receptors were equally efficient in supporting full differentiation of the EpoR-/- progenitors into erythroid colonies in vitro. Therefore, there is no requirement for an EpoR-unique signal in erythroid differentiation; EpoR signaling has no instructive role in red blood cell differentiation. A synergistic interaction between EpoR and c-kit is essential for the production of normal numbers of red blood cells, as demonstrated by the severe anemia of mice mutant for either c-kit or its ligand, stem cell factor. We show that the addition of stem cell factor potentiates the ability of the PrlR to support differentiation of both EpoR-/- and wild-type CFU-e progenitors. This synergism is quantitatively equivalent to that observed between c-kit and EpoR. Therefore, there is no requirement for an EpoR-unique signal in the synergistic interaction between c-kit and EpoR.