Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival

Mark A. Guthridge, Frank C. Stomski, Emma F. Barry, Wendy Winnall, Joanna M. Woodcock, Barbara J. McClure, Mara Dottore, Michael C. Berndt, Angel F. Lopez

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Abstract

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 β(c). This promotes the association of phospho-Ser-585 of β(c) with 14-3-3 and the p85 sub-unit 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.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalMolecular Cell
Volume6
Issue number1
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Guthridge, M. A., Stomski, F. C., Barry, E. F., Winnall, W., Woodcock, J. M., McClure, B. J., ... Lopez, A. F. (2000). Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival. Molecular Cell, 6(1), 99-108. https://doi.org/10.1016/S1097-2765(05)00002-X