Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte colony-stimulating factor receptor.
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.
Fukunaga
R
R
Osaka Bioscience Institute, Japan.
Ishizaka-Ikeda
E
E
Nagata
S
S
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D019272:Leukocyte Elastase; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010196:Pancreatic Elastase / Q000096:biosynthesis; D009195:Peroxidase / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection
D007377:Interleukin-3; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011986:Receptors, Somatotropin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase