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https://hdl.handle.net/2440/8785
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Type: | Journal article |
Title: | Activating point mutations in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors suggest the involvement of beta subunit dimerization and cell type-specific molecules in signalling |
Author: | Jenkins, B. D'Andrea, R. Gonda, T. |
Citation: | The EMBO Journal, 1995; 14(17):4276-4287 |
Publisher: | IRL Press |
Issue Date: | 1995 |
ISSN: | 0261-4189 1460-2075 |
Statement of Responsibility: | Jenkins, B J ; D'andrea, R ; Gonda, T J |
Abstract: | We have combined retroviral expression cloning with random mutagenesis to identify two activating point mutations in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 by virtue of their ability to confer factor independence on the haemopoietic cell line, FDC-P1. One mutation (V449E) is located within the transmembrane domain and, by analogy with a similar mutation in the neu oncogene, may act by inducing dimerization of h beta c. The other mutation (I374N) lies in the extracellular, membrane-proximal portion of h beta c. Neither of these mutants, nor a previously described mutant of h beta c (FI delta, which has a small duplication in the extracellular region), was capable of inducing factor independence in CTLL-2 cells, while only V449E could induce factor independence in BAF-B03 cells. These results imply that the extracellular and transmembrane mutations act by different mechanisms. Furthermore, they imply that the mutants, and hence also wild-type h beta c, interact with cell type-specific signalling molecules. Models are presented which illustrate how these mutations may act and predict some of the characteristics of the putative receptor-associated signalling molecules. |
Keywords: | Hematopoietic Stem Cells Cell Line Animals Humans Mice Cell Transformation, Neoplastic Macromolecular Substances Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors, Interleukin-3 Receptors, Interleukin Recombinant Proteins DNA Primers Transfection Mutagenesis, Site-Directed Polymerase Chain Reaction Signal Transduction Cell Division Gene Expression Regulation Amino Acid Sequence Base Sequence Point Mutation Molecular Sequence Data Receptors, Interleukin-5 |
DOI: | 10.1002/j.1460-2075.1995.tb00102.x |
Published version: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC394511/ |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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