A mutation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 that leads to ligand independence and tumorigenicity.
The cytokines interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor bind with high affinity to a receptor complex that contains a ligand-specific alpha-chain and a common beta-chain, h beta c. We report here the isolation of a mutant form of h beta c, from growth factor-independent cells, that arose spontaneously after infection of a murine factor-dependent hematopoietic cell line (FDC-P1) with a retroviral h beta c expression construct. Analysis of this h beta c mutation shows that a small (37 amino acid) duplication of extracellular sequence that includes two conserved sequence motifs is sufficient to confer ligand-independent growth on these cells and lead to tumourigenicity. Because this is a conserved region in the cytokine receptor superfamily, our results suggest that the large family of cytokine receptors has the capacity to become oncogenically active.
D'Andrea
R
R
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Rayner
J
J
Moretti
P
P
Lopez
A
A
Goodall
G J
GJ
Gonda
T J
TJ
Vadas
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009154:Mutation; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D016185:Receptors, Interleukin-3 / Q000502:physiology*; D053649:Receptors, Interleukin-5
D007377:Interleukin-3; D015848:Interleukin-5; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor