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© The Rockefeller University Press,
0021-9525/1998//1041 $5.00
The Journal of Cell Biology, Volume 141, Number 4,
, 1998 1041-1051
Articles |
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
chain specifically interfered with EpoR signaling, an activity neither seen for the βc subunit of the receptor complex alone, nor for the chain of the closely related Interleukin-3 receptor. These results point to a novel role of the GM-R chain in defining cell type–specific functions of the GM-R.
Abbreviations used in this paper: AS, anemic serum; βc, common β chain; BPA, burst-promoting activity; cMGF, chicken myelomonocytic growth factor; Epo, erythropoietin; EpoR, erythropoietin receptor; GM-CSF, Granulocyte–Macrophage Colony-Stimulating Factor; GM-R, GM-CSF receptor; GM-R, GM-R chain; IL, interleukin; IRES, internal ribosome entry site; ts, temperature sensitive.
O. Wessely and E.-M. Deiner contributed equally to this work.
O. Wessely's present address is Howard Hughes Medical Institute, University of California, Los Angeles, CA.
K.C. Lim's present address is Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, IL 60208.
G. Mellitzer's present address is National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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