Signal transduction mediated by growth hormone receptor and its chimeric molecules with the granulocyte colony-stimulating factor receptor.
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.
Ishizaka-Ikeda
E
E
Osaka Bioscience Institute, Japan.
Fukunaga
R
R
Wood
W I
WI
Goeddel
D V
DV
Nagata
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011817:Rabbits; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D007377:Interleukin-3; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013006:Growth Hormone; D004247:DNA; D066246:ErbB Receptors