Low-affinity placenta-derived receptors for human granulocyte-macrophage colony-stimulating factor can deliver a proliferative signal to murine hemopoietic cells.
Retrovirally mediated introduction of a cDNA encoding a placenta-derived low-affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) into murine FDC-P1 hemopoietic cells allowed these cells to proliferate when stimulated by human GM-CSF. The expressed human receptors on cloned lines were of low affinity (Kd = 4-6 nM), were internalized, and did not interact with endogenous GM-CSF receptors. Concentrations of human GM-CSF of 6.5-13 nM were required to stimulate 50% maximal colony formation versus a concentration of murine GM-CSF of 6 pM; this difference is comparable with the difference in relative affinities of the human and murine receptors for their respective ligands. If maintained in murine GM-CSF, cells able to bind or respond to human GM-CSF were rapidly lost due to transcriptional inactivation of the inserted cDNA. The observations indicate that low-affinity receptors for human GM-CSF can deliver a proliferative signal in appropriate cells and that the signaling mechanisms are not species-specific.
Metcalf
D
D
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nicola
N A
NA
Gearing
D P
DP
Gough
N M
NM
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor; D015398:Signal Transduction; D014158:Transcription, Genetic
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor