Abstract
Granulocyte colony-stimulating factor (G-CSF) is a cytokine that regulates the proliferation and differentiation of neutrophils. The G-CSF receptor (G-CSFR) is a member of the hemopoietic growth factor receptor family. A G-CSFR expression plasmid was introduced into interleukin-3 (IL-3)-dependent mouse myeloid precursor FDC-P1 cells that normally do not respond to G-CSF. G-CSF stimulated proliferation of the transformants, down-regulated Thy-1 and F4/80 antigens on the cell surface, and induced expression of neutrophil-specific genes such as myeloperoxidase (MPO) and leukocyte elastase. On the other hand, neither granulocyte/macrophage colony-stimulating factor (GM-CSF) nor IL-3 induced MPO gene expression, but they inhibited G-CSFR-mediated MPO gene expression. These results suggested that the G-CSFR, but not the IL-3/GM-CSF receptors, transduced the neutrophilic differentiation signal into cells. Mutational analysis of the G-CSFR indicated that the N-terminal region of its cytoplasmic domain is sufficient to transduce the proliferation signal into cells, while the C-terminal region plays an essential role in transducing the differentiation signal.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Blotting, Northern
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Cell Differentiation
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Cell Division
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Cell Line
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DNA Replication / drug effects
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Gene Expression / drug effects
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Granulocyte Colony-Stimulating Factor / pharmacology*
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Hematopoietic Stem Cells
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Humans
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Interleukin-3 / pharmacology*
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Leukocyte Elastase
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Oligodeoxyribonucleotides
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Pancreatic Elastase / biosynthesis
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Peroxidase / biosynthesis
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Polymerase Chain Reaction
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism
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Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
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Receptors, Granulocyte Colony-Stimulating Factor / drug effects
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Receptors, Granulocyte Colony-Stimulating Factor / metabolism*
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Receptors, Somatotropin / biosynthesis
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Signal Transduction
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Transfection
Substances
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Interleukin-3
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Oligodeoxyribonucleotides
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RNA, Messenger
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Receptors, Granulocyte Colony-Stimulating Factor
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Receptors, Somatotropin
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Recombinant Fusion Proteins
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Recombinant Proteins
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Granulocyte Colony-Stimulating Factor
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Granulocyte-Macrophage Colony-Stimulating Factor
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Peroxidase
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Pancreatic Elastase
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Leukocyte Elastase