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https://hdl.handle.net/2440/9308
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Type: | Journal article |
Title: | Constitutive mutants of the GM-CSF receptor reveal multiple pathways leading to myeloid cell survival, proliferation, and granulocyte-macrophage differentiation |
Author: | Brown, A. Peters, M. D'Andrea, R. Gonda, T. |
Citation: | Blood, 2004; 103(2):507-516 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2004 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Anna L. Brown, Michelle Peters, Richard J. D'Andrea, and Thomas J. Gonda |
Abstract: | Activation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) family of receptors promotes the survival, proliferation, and differentiation of cells of the myeloid compartment. Several signaling pathways are activated downstream of the receptor, however it is not clear how these induce specific biologic outcomes. We have previously identified 2 classes of constitutively active mutants of the shared signaling subunit, human (h) betac, of the human GM-CSF/interleukin-3 (IL-3)/IL-5 receptors that exhibit different modes of signaling. In a factor-dependent bipotential myeloid cell line, FDB1, an activated mutant containing a substitution in the transmembrane domain (V449E) induces factor-independent proliferation and survival, while mutants in the extracellular domain induce factor-independent granulocyte-macrophage differentiation. Here we have used further mutational analysis to demonstrate that there are nonredundant functions for several regions of the cytoplasmic domain with regard to mediating proliferation, viability, and differentiation, which have not been revealed by previous studies with the wild-type GM-CSF receptor. This unique lack of redundancy has revealed an association of a conserved membrane-proximal region with viability signaling and a critical but distinct role for tyrosine 577 in the activities of each class of mutant. |
Keywords: | Granulocytes Bone Marrow Cells Cell Line Macrophages Animals Humans Mice Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors, Interleukin-3 Receptors, Interleukin DNA Primers Transfection Signal Transduction Cell Division Cell Differentiation Cell Survival Base Sequence Mutation Receptors, Interleukin-5 |
DOI: | 10.1182/blood-2003-05-1435 |
Published version: | http://dx.doi.org/10.1182/blood-2003-05-1435 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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