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|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|
|Citation:||EMBO Journal, 1995; 14(17):4276-4287|
|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|
|Appears in Collections:||Medicine publications|
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