The Human Granulocyte - Macrophage Colony - Stimulating Factor ( GM - CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated

The granulocyte-macrophage colony-stimulating factor GM-CSF. The preformed complex required only the extracellular regions of GMRa and bc , as shown by the ability of (GM-CSF) receptor is expressed on normal and malignant hematopoietic cells as well as on cells from other organs soluble bc to associate with membrane-anchored GMRa or soluble GMRa. Kinetic experiments on eosinophils and in which it transduces a variety of functions. Despite the widespread expression and pleiotropic nature of the GMmonocytes with radiolabeled GM-CSF, IL-3, and IL-5 showed association characteristics unique to GM-CSF. Significantly, CSF receptor, little is known about its assembly and activation mechanism. Using a combination of biochemical and receptor phosphorylation experiments showed that not only GM-CSF but also IL-3 and IL-5 stimulated the phosphorylafunctional approaches, we have found that the human GMCSF receptor exists as an inducible complex, analogous to tion of GMRa-associated bc . These results indicate a pattern of assembly of the heterodimeric GM-CSF receptor that is the interleukin-3 (IL-3) receptor, and also as a preformed complex, unlike the IL-3 receptor or indeed other members unique among receptors of the cytokine receptor superfamily. These results also suggest that the preformed GM-CSF of the cytokine receptor superfamily. We found that monoclonal antibodies to the GM-CSF receptor a chain (GMRa) receptor complex mediates the instantaneous binding of GM-CSF and is a target of phosphorylation by IL-3 and IL-5, and to the common b chain of the GM-CSF, IL-3, and IL-5 receptors (bc ) immunoprecipitated both GMRa and bc from raising the possibility that some of the biologic activities of IL-3 and IL-5 are mediated through the GM-CSF receptor the surface of primary myeloid cells, myeloid cell lines, and transfected cells in the absence of GM-CSF. Further associacomplex. q 1997 by The American Society of Hematology. tion of the two chains could be induced by the addition of