Alternative forms of the human G-CSF receptor function in growth signal transduction.
Two forms of the human granulocyte colony-stimulating factor (G-CSF) receptor (HuG-CSFR), differing only at the carboxyl terminus, were recently identified by cDNA cloning. In this report we show that transfection and subsequent expression of either cDNA clone in the interleukin-3 (IL-3)-dependent murine cell line BAF/BO3 converts the cells to G-CSF-responsiveness. The transfected cells bound HuG-CSF in a manner indistinguishable from the native receptors. Expression of a mutant form of the HuG-CSFR, with a deletion in the cytoplasmic domain, in BAF/BO3 cells failed to convert the cells to HuG-CSF-responsiveness. In a similar manner, expression of these two HuG-CSFRs in the interleukin-6 (IL-6)-dependent murine hybridoma B9 resulted in the ability of these cells to grow in HuG-CSF [corrected]. These results strongly suggest that sequences in the first 96 amino acids of the cytoplasmic domain of the HuG-CSFR are required for signal transduction in response to ligand binding.
Ziegler
S F
SF
Immunex Research and Development Corp., Seattle, WA 98101.
Davis
T
T
Schneringer
J A
JA
Franklin
T L
TL
Tough
T W
TW
Teepe
M
M
Larsen
A
A
Williams
D E
DE
Smith
C A
CA
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006825:Hybridomas; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D015850:Interleukin-6; D015345:Oligonucleotide Probes; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor