Ishizaka-Ikeda E, Fukunaga R, Wood W I, Goeddel D V, Nagata S
Osaka Bioscience Institute, Japan.
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):123-7. doi: 10.1073/pnas.90.1.123.
The granulocyte colony-stimulating factor receptor (G-CSF-R) and growth hormone receptor (GH-R) belong to the cytokine receptor family and have some similarity in the cytokine receptor-homologous (CRH) domain of the extracellular region. Among members of this family, the G-CSF-R and GH-R seem to function as homodimers. Previously, we showed that mouse myeloid precursor FDC-P1 cells expressing the G-CSF-R can respond to G-CSF for growth. Here we show that the GH-R can also transduce the growth signal in FDC-P1 cells in the range 10 pM-100 nM GH. At a higher concentration of GH, GH did not promote the growth of the transformant cells. A series of chimeric receptor cDNAs between the G-CSF-R and GH-R cDNAs was constructed by exon swapping and was expressed in FDC-P1 cells. A ligand-binding assay with transformants expressing chimeric receptors indicated that the entire CRH domain is necessary for specific binding of the ligand. Although the transmembrane and cytoplasmic regions of the G-CSF-R and GH-R have no apparent similarity, these regions were interchangeable, resulting in growth-signal transduction in FDC-P1 cells.
粒细胞集落刺激因子受体（G-CSF-R）和生长激素受体（GH-R）属于细胞因子受体家族，在细胞外区域的细胞因子受体同源（CRH）结构域具有一定相似性。在该家族成员中，G-CSF-R和GH-R似乎以同二聚体形式发挥作用。此前，我们发现表达G-CSF-R的小鼠髓系前体细胞FDC-P1能够对G-CSF作出生长反应。在此我们表明，GH-R在10 pM至100 nM的GH浓度范围内也能在FDC-P1细胞中传导生长信号。在更高浓度的GH下，GH不会促进转化细胞的生长。通过外显子交换构建了一系列G-CSF-R和GH-R cDNA之间的嵌合受体cDNA，并在FDC-P1细胞中表达。对表达嵌合受体的转化体进行配体结合试验表明，整个CRH结构域对于配体的特异性结合是必需的。尽管G-CSF-R和GH-R的跨膜区和胞质区没有明显的相似性，但这些区域是可互换的，从而在FDC-P1细胞中实现生长信号转导。
