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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 |
Published version: | http://dx.doi.org/10.1182/blood-2008-12-164004 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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