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https://hdl.handle.net/2440/76600
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Type: | Journal article |
Title: | The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling |
Author: | Broughton, S. Dhagat, U. Hercus, T. Nero, T. Grimbaldeston, M. Bonder, C. Lopez, A. Parker, M. |
Citation: | Immunological Reviews, 2012; 250(1):277-302 |
Publisher: | Munksgaard Int Publ Ltd |
Issue Date: | 2012 |
ISSN: | 0105-2896 1600-065X |
Statement of Responsibility: | Sophie E. Broughton, Urmi Dhagat, Timothy R. Hercus, Tracy L. Nero, Michele A. Grimbaldeston, Claudine S. Bonder, Angel F. Lopez, Michael W. Parker |
Abstract: | Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are members of a discrete family of cytokines that regulates the growth, differentiation, migration and effector function activities of many hematopoietic cells and immunocytes. These cytokines are involved in normal responses to infectious agents, bridging innate and adaptive immunity. However, in certain cases, the overexpression of these cytokines or their receptors can lead to excessive or aberrant initiation of signaling resulting in pathological conditions, with chronic inflammatory diseases and myeloid leukemias the most notable examples. Recent crystal structures of the GM-CSF receptor ternary complex and the IL-5 binary complex have revealed new paradigms of cytokine receptor activation. Together with a wealth of associated structure-function studies, they have significantly enhanced our understanding of how these receptors recognize cytokines and initiate signals across cell membranes. Importantly, these structures provide opportunities for structure-based approaches for the discovery of novel and disease-specific therapeutics. In addition, recent biochemical evidence has suggested that the GM-CSF/IL-3/IL-5 receptor family is capable of interacting productively with other membrane proteins at the cell surface. Such interactions may afford additional or unique biological activities and might be harnessed for selective modulation of the function of these receptors in disease. |
Keywords: | crystal structures cytokine granulocyte–macrophage colony-stimulating factor interleukin-3 interleukin-5 receptor signaling |
Rights: | © 2012 John Wiley & Sons A/S |
DOI: | 10.1111/j.1600-065X.2012.01164.x |
Published version: | http://dx.doi.org/10.1111/j.1600-065x.2012.01164.x |
Appears in Collections: | Aurora harvest 4 Microbiology and Immunology publications |
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