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Type: Journal article
Title: Expression of activated mutants of the human interleukin-3/interleukin-5/granulocyte-macrophage colony-stimulating factor receptor common beta subunit in primary hematopoietic cells induces factor-independent proliferation and differentiation.
Author: McCormack, M.
Gonda, T.
Citation: Blood, 1997; 90(4):1471-1481
Publisher: W B SAUNDERS CO
Issue Date: 1997
ISSN: 0006-4971
Abstract: To date, several activating mutations have been discovered in the common signal-transducing subunit (h(beta)c) of the receptors for human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Two of these, FIdelta and I374N, result in a 37 amino acid duplication and a single amino acid substitution in the extracellular domain of h(beta)c, respectively. A third, V449E, results in a single amino acid substitution in the transmembrane domain. Previous studies comparing the activity of these mutants in different hematopoietic cell lines imply that the transmembrane and extracellular mutations act by different mechanisms and suggest the requirement for cell type-specific molecules in signalling. To characterize the ability of these mutant h(beta)c subunits to mediate growth and differentiation of primary cells and hence investigate their oncogenic potential, we have expressed all three mutants in primary murine hematopoietic cells using retroviral transduction. It is shown that, whereas expression of either extracellular h(beta)c mutant confers factor-independent proliferation and differentiation on cells of the neutrophil and monocyte lineages only, expression of the transmembrane mutant does so on these lineages as well as the eosinophil, basophil, megakaryocyte, and erythroid lineages. Factor-independent myeloid precursors expressing the transmembrane mutant display extended proliferation in liquid culture and in some cases yielded immortalized cell lines.
Keywords: Liver
Hematopoietic Stem Cells
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Receptors, Interleukin-3
Receptors, Interleukin
Recombinant Proteins
Signal Transduction
Cell Division
Binding Sites
Protein Conformation
Receptors, Interleukin-5
DOI: 10.1182/blood.v90.4.1471
Appears in Collections:Aurora harvest 4
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