Expression of Activated Mutants of the Human Interleukin-3/Interleukin-5/ Granulocyte-Macrophage Colony-Stimulating Factor Receptor Common b Subunit in Primary Hematopoietic Cells Induces Factor-Independent Proliferation and Differentiation

To date, several activating mutations have been discovered cells and hence investigate their oncogenic potential, we in the common signal-transducing subunit (hbc) of the rehave expressed all three mutants in primary murine hematoceptors for human granulocyte-macrophage colony-stimupoietic cells using retroviral transduction. It is shown that, lating factor, interleukin-3, and interleukin-5. Two of these, whereas expression of either extracellular hbc mutant conFID and I374N, result in a 37 amino acid duplication and a fers factor-independent proliferation and differentiation on single amino acid substitution in the extracellular domain cells of the neutrophil and monocyte lineages only, expresof hbc, respectively. A third, V449E, results in a single amino sion of the transmembrane mutant does so on these linacid substitution in the transmembrane domain. Previous eages as well as the eosinophil, basophil, megakaryocyte, studies comparing the activity of these mutants in different and erythroid lineages. Factor-independent myeloid precurhematopoietic cell lines imply that the transmembrane and sors expressing the transmembrane mutant display exextracellular mutations act by different mechanisms and tended proliferation in liquid culture and in some cases suggest the requirement for cell type-specific molecules in yielded immortalized cell lines. signalling. To characterize the ability of these mutant hbc q 1997 by The American Society of Hematology. subunits to mediate growth and differentiation of primary