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 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.
Guthridge
M A
MA
Department of Human Immunology, The Hanson Centre for Cancer Research, IMVS, Adelaide, South Australia, Australia.
Stomski
F C
FC
Barry
E F
EF
Winnall
W
W
Woodcock
J M
JM
McClure
B J
BJ
Dottore
M
M
Berndt
M C
MC
Lopez
A F
AF
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006413:Hematopoietic System / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D007377:Interleukin-3; D011506:Proteins; D016185:Receptors, Interleukin-3; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases