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

• Published in: Molecular cell Vol. 6; no. 1; pp. 99 - 108
• Main Authors: Guthridge, Mark A., Stomski, Frank C., Barry, Emma F., Winnall, Wendy, Woodcock, Joanna M., McClure, Barbara J., Dottore, Mara, Berndt, Michael C., Lopez, Angel F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2000
• Subjects: 14-3-3 Proteins; Amino Acid Sequence; Animals; Binding Sites; Cell Division; Cell Line; Cell Survival; Cyclic AMP-Dependent Protein Kinases - metabolism; Hematopoietic System - cytology; Hematopoietic System - immunology; Hematopoietic System - metabolism; interleukin 3 receptors; Interleukin-3 - pharmacology; Mice; Mutagenesis, Site-Directed; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proteins - metabolism; Receptors, Interleukin-3 - chemistry; Receptors, Interleukin-3 - genetics; Receptors, Interleukin-3 - metabolism; Serine - metabolism; Signal Transduction; Tyrosine 3-Monooxygenase
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(05)00002-X

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 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.