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Science 29 September 1989:
Vol. 245. no. 4925, pp. 1493 - 1496
DOI: 10.1126/science.2789432
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Articles

Science, Vol 245, Issue 4925, 1493-1496
Copyright © 1989 by American Association for the Advancement of Science

articles

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

CE Dunbar, TM Browder, JS Abrams, and AW Nienhuis

Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.

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.


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