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Volume 271, Number 48, Issue of November 29, 1996 pp. 30386-30391
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Functional Replacement of Cytokine Receptor Extracellular Domains by Leucine Zippers

(Received for publication, July 9, 1996, and in revised form, September 12, 1996)

From the Molecular Biology Department, DNAX Research Institute, Palo Alto, California 94304

Granulocyte-macrophage colony-stimulating factor receptor signals by a complex which includes the ligand and two different receptor subunits: a low affinity  receptor binding chain (granulocyte-macrophage colony-stimulating factor receptor  subunit (GM-R)) and a signal-transducing  chain (GM-R). To investigate two unresolved issues in the initiation of signaling, the role of receptor extracellular domains and receptor stoichiometry, we replaced the mouse GM-R and GM-R extracellular domains with the leucine zipper domain of either the Fos or Jun molecule. We co-transfected combinations of chimeric receptors into Ba/F3 cells and found that both simple heterodimers of the GM-R and GM-R intracellular domains and homodimers of the GM-R intracellular domain signaled for proliferation. Surprisingly, homodimers of the GM-R intracellular domain also signaled for prevention of apoptosis in transfected cells. We similarly engineered dimers of the intracellular domain of the human interferon  receptor  subunit and found that homodimers of the intracellular domain signaled for proliferation. When Fos peptide was added to Ba/F3 cells expressing the human interferon  receptor  subunit construct, thereby preventing homodimer formation, the cells no longer proliferated in the absence of mouse interleukin 3.

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