Mammalian granulocyte-macrophage colony-stimulating factor receptor expressed in primary avian hematopoietic progenitors: lineage-specific regulation of proliferation and differentiation.
The cytokine Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) regulates proliferation, differentiation, and apoptosis during myelopoiesis and erythropoiesis. Structure-function relationships of GM-CSF interactions with its receptor (GM-R), the biochemistry of GM-R signal transduction, and GM-CSF action in vivo are relatively well understood. Much less is known, however, about GM-R function in primary hematopoietic cells. In this paper we show that expression of the human GM-R in a heterologous cell system (primary avian erythroid and myeloid cells) confirms respective results in murine or human cell lines, but also provides new insights how the GM-R regulates progenitor proliferation and differentiation. As expected, the hGM-CSF stimulated myeloid progenitor proliferation and differentiation and enhanced erythroid progenitor proliferation during terminal differentiation. In the latter cells, however, the hGM-R only partially substituted for the activities of the erythropoietin receptor (EpoR). It failed to replace the EpoR in its cooperation with c-Kit to induce long-term proliferation of erythroid progenitors. Furthermore, the hGM-R alpha chain specifically interfered with EpoR signaling, an activity neither seen for the betac subunit of the receptor complex alone, nor for the alpha chain of the closely related Interleukin-3 receptor. These results point to a novel role of the GM-R alpha chain in defining cell type-specific functions of the GM-R.
Wessely
O
O
Institute for Molecular Pathology, A-1030 Vienna, Austria.
Deiner
E M
EM
Lim
K C
KC
Mellitzer
G
G
Steinlein
P
P
Beug
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002642:Chick Embryo; D004900:Erythroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology; D005347:Fibroblasts; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D008322:Mammals; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D012190:Retroviridae; D015398:Signal Transduction; D014162:Transfection
D006454:Hemoglobins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor