Swapping between Fas and granulocyte colony-stimulating factor receptor.
Fas belongs to the tumor necrosis factor/nerve growth factor receptor family. The Fas ligand binds to its receptor, Fas, and induces apoptosis in Fas-bearing cells. The granulocyte colony-stimulating factor receptor (G-CSFR) is a member of the hemopoietic growth factor receptor family. G-CSF induces its dimerization and regulates the proliferation and differentiation of neutrophilic granulocytes. We constructed hybrid receptors between Fas and G-CSFR and expressed them in the mouse T cell line WR19L or the mouse myeloid interleukin-3-dependent FDC-P1 cell line. The Fas ligand or an agonistic anti-Fas antibody stimulated proliferation of the FDC-P1 transformants expressing a chimera consisting of the Fas extracellular and G-CSFR cytoplasmic regions. On the other hand, G-CSF could not induce apoptosis in the transformants expressing the chimera consisting of the G-CSFR extracellular and Fas cytoplasmic regions, but these cells were killed by a polyclonal antibody against G-CSFR. These results indicated that receptors belonging to different receptor families can be functionally exchanged and confirm that a homodimer of G-CSFR can transduce the growth signal, whereas Fas must be oligomerized (probably trimerized) to transduce the apoptotic signal.
Takahashi
T
T
Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Japan.
Tanaka
M
M
Ogasawara
J
J
Suda
T
T
Murakami
H
H
Nagata
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D053222:Fas Ligand Protein; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016399:Lymphoma, T-Cell; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes; D014162:Transfection; D019014:fas Receptor / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D016179:Granulocyte Colony-Stimulating Factor