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

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 subu nit of PI 3-K. Mutation of Ser-585 specifically impairs the PI 3-K signalin g pathway and reduces cell survival in response to IL-3. These results defi ne a distinct IL-3 receptor-mediated survival pathway regulated by site-spe cific receptor serine phosphorylation and 14-3-3 binding and suggest that t his novel mode of signaling may be utilized by disparate transmembrane rece ptors that have as a common theme the transduction of survival signals.