Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/58824
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Type: Journal article
Title: The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease
Author: Hercus, T.
Thomas, D.
Guthridge, M.
Ekert, P.
King-Scott, J.
Parker, M.
Lopez, A.
Citation: Blood, 2009; 114(7):1289-1298
Publisher: Amer Soc Hematology
Issue Date: 2009
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Timothy R. Hercus, Daniel Thomas, Mark A. Guthridge, Paul G. Ekert, Jack King-Scott, Michael W. Parker, and Angel F. Lopez
Abstract: Already 20 years have passed since the cloning of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor {alpha}-chain, the first member of the GM-CSF/interleukin (IL)–3/IL-5 family of hemopoietic cytokine receptors to be molecularly characterized. The intervening 2 decades have uncovered a plethora of biologic functions transduced by the GM-CSF receptor (pleiotropy) and revealed distinct signaling networks that couple the receptor to biologic outcomes. Unlike other hemopoietin receptors, the GM-CSF receptor has a significant nonredundant role in myeloid hematologic malignancies, macrophage-mediated acute and chronic inflammation, pulmonary homeostasis, and allergic disease. The molecular mechanisms underlying GM-CSF receptor activation have recently been revealed by the crystal structure of the GM-CSF receptor complexed to GM-CSF, which shows an unexpected higher order assembly. Emerging evidence also suggests the existence of intracellular signosomes that are recruited in a concentration-dependent fashion to selectively control cell survival, proliferation, and differentiation by GM-CSF. These findings begin to unravel the mystery of cytokine receptor pleiotropy and are likely to also apply to the related IL-3 and IL-5 receptors as well as other heterodimeric cytokine receptors. The new insights in GM-CSF receptor activation have clinical significance as the structural and signaling nuances can be harnessed for the development of new treatments for malignant and inflammatory diseases.
Keywords: Lung
Macrophages
Animals
Humans
Leukemia, Myeloid
Hypersensitivity
Acute Disease
Chronic Disease
Inflammation
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Signal Transduction
Cell Differentiation
Cell Proliferation
Cell Survival
Structure-Activity Relationship
Homeostasis
Rights: © 2009 by The American Society of Hematology
DOI: 10.1182/blood-2008-12-164004
Appears in Collections:Aurora harvest 5
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