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• W1486705501 startingPage "231" @default.
• W1486705501 abstract "Granulocyte-macrophage colony stimulating factor (GM-CSF), Interleukin-3 (IL-3) and Interleukin-5 (IL-5) have overlapping, pleiotropic effects on hematopoietic cells, including neutrophils, eosinophils, monocytes and early progenitor cells. The high-affinity receptors for human GM-CSF, IL-3, and IL-5 share a common β-subunit (hβc), which is essential for signalling and plays a major role in recruiting intracellular signalling molecules. While activation of the cytoplasmic tyrosine kinase JAK2 appears to be the initiating event for signalling, the immediate events that trigger this are still unclear. We have isolated a number of activated mutants of hβc, which can be grouped into classes defined by their state of receptor phosphorylation, their requirement for α subunit as a cofactor, and their activities in primary cells and cell lines. We discuss these findings with regard to the stoichiometry, activation, and signalling of the normal GM-CSF/IL-3/IL-5 receptor complexes. Specifically, this work has implications for the role of the ligand-specific α-subunits in initiating the signalling through the β-subunit, the role of β subunit dimerization as a receptor trigger, and the function of receptor tyrosine phosphorylation in generating growth and survival signals. Based on the properties of the activated mutants and the recent structures of erythropoietin receptor (Epo-R) complexes, we propose a model in which (1) activation of hβc can occur via alternative states that differ with respect to stoichiometry and subunit assembly, but which all mediate proliferative responses, and (2) each of the different classes of activated mutants mimics one of these alternative states." @default.
• W1486705501 created "2016-06-24" @default.
• W1486705501 creator A5040177912 @default.
• W1486705501 creator A5076782260 @default.
• W1486705501 date "2000-03-01" @default.
• W1486705501 modified "2023-10-16" @default.
• W1486705501 title "A model for assembly and activation of the GM-CSF, IL-3 and IL-5 receptors" @default.
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