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The  Chain of the Interleukin-3 Receptor Functionally Associates With the Erythropoietin Receptor
Paul T. Jubinsky,
Oleg I. Krijanovski,
David G. Nathan,
Jan Tavernier, and
Colin A. Sieff
From the Divisions of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA; the Department of Pediatrics and Immunology, Harvard Medical School, Boston, MA; and the Department of Medical Protein Chemistry, University of Ghent, Ghent, Belgium.
Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF ) receptors share a common  chain (c), and both cytokines enhance erythropoietin (Epo)-dependent in vitro erythropoiesis by primary hematopoietic progenitors and factor-dependent cells. These data suggest that the Epo receptor and c may functionally interact. To determine whether such interactions can be documented, we studied a murine factor-dependent cell line (Ba/F3), which endogenously expresses IL-3R. First, Ba/F3 cells were transfected with murine EpoR, making them responsive to both IL-3 and Epo. Next, the EpoR expressing cells were transfected with murine c. This resulted in an enhanced sensitivity of these cells to Epo, which was especially pronounced at low Epo concentrations. Ba/F3-EpoR were then treated with antisense oligodeoxynucleotides to the murine . Control sense and nonsense had no effect on Epo-dependent growth, but the antisense markedly and specifically inhibited Epo-dependent growth. In contrast, the antisense did not affect -globin message levels (another Epo-responsive effect in these cells) detectable by Northern blot. Finally, Western blot analysis of proteins immunoprecipitated from cells expressing both receptors with antibody against and blotted with antibody against EpoR, or immunoprecipitated with antibody against EpoR and blotted with antibody against , showed that EpoR and coimmunoprecipitate. These data show that the chain functionally and physically associates with the EpoR. This suggests that these cytokine receptors exist as a large supercomplex and offers the first molecular explanation for the synergistic effects of IL-3 and GM-CSF with Epo during erythropoiesis.
Blood, Vol. 90 No. 5 (September 1), 1997:
pp. 1867-1873
© 1997 by The American Society of Hematology.
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