Takahashi T, Tanaka M, Ogasawara J, Suda T, Murakami H, Nagata S
Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Japan.
J Biol Chem. 1996 Jul 19;271(29):17555-60. doi: 10.1074/jbc.271.29.17555.
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.
Fas属于肿瘤坏死因子/神经生长因子受体家族。Fas配体与其受体Fas结合，并诱导表达Fas的细胞发生凋亡。粒细胞集落刺激因子受体（G-CSFR）是造血生长因子受体家族的成员。G-CSF诱导其二聚化，并调节嗜中性粒细胞的增殖和分化。我们构建了Fas与G-CSFR之间的杂交受体，并在小鼠T细胞系WR19L或小鼠髓样白细胞介素-3依赖的FDC-P1细胞系中表达。Fas配体或抗Fas激动性抗体刺激表达由Fas胞外区和G-CSFR胞质区组成的嵌合体的FDC-P1转化体增殖。另一方面，G-CSF不能诱导表达由G-CSFR胞外区和Fas胞质区组成的嵌合体的转化体凋亡，但这些细胞被抗G-CSFR多克隆抗体杀死。这些结果表明，属于不同受体家族的受体可以进行功能交换，并证实G-CSFR的同型二聚体可以转导生长信号，而Fas必须寡聚化（可能三聚化）才能转导凋亡信号。
