COOH-terminal-modified interleukin-3 is retained intracellularly and stimulates autocrine growth

Science. 1989 Sep 29;245(4925):1493-6. doi: 10.1126/science.2789432.

Abstract

Autocrine growth due to dysregulated growth factor production may have a role in the development of neoplasia. Whether autocrine growth is stimulated by growth factor secretion in an autocrine loop or by intracellular binding of the growth factor to a receptor has been unclear. The carboxyl-terminus coding sequence for murine interleukin-3 (IL-3) was extended with an oligonucleotide encoding a four-amino acid endoplasmic reticulum retention signal. IL-3-dependent hematopoietic cells became growth factor-independent when the modified IL-3 gene was introduced by retroviral gene transfer, despite lack of secretion of the modified IL-3. Hence autocrine growth can occur as a result of the intracellular action of a growth factor and this mechanism may be important in neoplastic and normal cells.

MeSH terms

  • Animals
  • Cell Division* / drug effects
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Clone Cells
  • Interleukin-3 / genetics
  • Interleukin-3 / metabolism
  • Interleukin-3 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Interleukin-3
  • Recombinant Fusion Proteins