COOH-terminal-modified interleukin-3 is retained intracellularly and stimulates autocrine growth.
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.
Dunbar
C E
CE
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Browder
T M
TM
Abrams
J S
JS
Nienhuis
A W
AW
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002999:Clone Cells; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D007377:Interleukin-3; D011993:Recombinant Fusion Proteins