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

Abstract

AbstractThe cytokines interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor bind with high affinity to a receptor complex that contains a ligand-specific a-chain and a common β-chain, hβc. We report here the isolation of a mutant form of hβc, from growth factor-independent cells, that arose spontaneously after infection of a murine factor-dependent hematopoietic cell line (FDC-P1) with a retroviral hβc expression construct. Analysis of this hβc 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.