Site-Specific Serine Phosphorylation of the IL-3 Receptor Is Required for Hemopoietic Cell Survival

Department of Human Immunology, The Hanson Centre for Cancer Research, IMVS, Adelaide, South Australia, Australia.
Molecular Cell (Impact Factor: 14.02). 08/2000; 6(1):99-108. DOI: 10.1016/S1097-2765(05)00002-X
Source: PubMed


In the hemopoietic compartment, IL-3, GM-CSF, and IL-5 receptors are major transducers of survival signals; however, the receptor-proximal events that determine this vital function have not been defined. We have found that IL-3 stimulation induces phosphorylation of Ser-585 of beta(c). This promotes the association of phospho-Ser-585 of beta(c) with 14-3-3 and the p85 subunit of PI 3-K. Mutation of Ser-585 specifically impairs the PI 3-K signaling pathway and reduces cell survival in response to IL-3. These results define a distinct IL-3 receptor-mediated survival pathway regulated by site-specific receptor serine phosphorylation and 14-3-3 binding and suggest that this novel mode of signaling may be utilized by disparate transmembrane receptors that have as a common theme the transduction of survival signals.

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Available from: Jo Woodcock, May 07, 2014
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    • "Production and purification of the histidine-tagged recombinant βic protein encompassing amino acids 445-881 of the intracellular domain of GM-CSF/IL-3 βc has been previously described [23], [28]. "
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    PLoS ONE 08/2013; 8(8):e71337. DOI:10.1371/journal.pone.0071337 · 3.23 Impact Factor
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    • "The activation of cell surface receptors like IL-3 and GM-CSF receptors ultimately regulates the Bcl-2 family of proteins to control whether a cell remains viable or commits to apoptosis (Chao et al. 1998; Vaux et al. 1988; Ekert et al. 2006). The observation that low concentrations of GM-CSF can maintain the viability of cytokine-dependent cells while not stimulating cell proliferation (Begley et al. 1986; Guthridge et al. 2000) suggests that it is possible for ligand– receptor binding to activate signaling pathways that regulate apoptosis, while not engaging those that drive proliferation and probably involves the phosphorylation of bc Ser585 (Guthridge et al. 2004, 2006). The flip side of survival signals transduced by GM-CSF and IL-3 is the initiation of apoptosis when these cytokine signals are lost. "
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