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

doi:10.1016/S1097-2765(05)00002-X

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

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

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 language	English
Pages (from-to)	99-108
Number of pages	10
Journal	Molecular Cell
Volume	6
Issue number	1
DOIs	https://doi.org/10.1016/S1097-2765(05)00002-X
Publication status	Published or Issued - 2000
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(05)00002-X

Cite this

@article{d5c92e54a71d4b15871d1894eefe32d1,

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

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.",

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

note = "Funding Information: We thank Dr. Tom Gonda for the CTL-EN cells and the pRUFHygro vector, Dr. Cristina Mitchell, and Professor Bruce Kemp for helpful advice and discussions and Anna Nitschke for excellent secretarial assistance. We thank Dr. Christopher J. Bagley for mass spectrometer analysis of phosphorylated peptides. We also thank Drs. Tom Gonda, Sharad Kumar, and Binks Wattenberg for critical reading of the manuscript. This work was supported by grants from the National Health and Medical Research Council of Australia and the Anti-Cancer Foundation of South Australia (ACF). J. M. W. is supported by a fellowship from the ACF.",

year = "2000",

doi = "10.1016/S1097-2765(05)00002-X",

language = "English",

volume = "6",

pages = "99--108",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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T1 - Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival

AU - Guthridge, Mark A.

AU - Stomski, Frank C.

AU - Barry, Emma F.

AU - Winnall, Wendy

AU - Woodcock, Joanna M.

AU - McClure, Barbara J.

AU - Dottore, Mara

AU - Berndt, Michael C.

AU - Lopez, Angel F.

N1 - Funding Information: We thank Dr. Tom Gonda for the CTL-EN cells and the pRUFHygro vector, Dr. Cristina Mitchell, and Professor Bruce Kemp for helpful advice and discussions and Anna Nitschke for excellent secretarial assistance. We thank Dr. Christopher J. Bagley for mass spectrometer analysis of phosphorylated peptides. We also thank Drs. Tom Gonda, Sharad Kumar, and Binks Wattenberg for critical reading of the manuscript. This work was supported by grants from the National Health and Medical Research Council of Australia and the Anti-Cancer Foundation of South Australia (ACF). J. M. W. is supported by a fellowship from the ACF.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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