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dc.contributor.authorHercus, T.-
dc.contributor.authorThomas, D.-
dc.contributor.authorGuthridge, M.-
dc.contributor.authorEkert, P.-
dc.contributor.authorKing-Scott, J.-
dc.contributor.authorParker, M.-
dc.contributor.authorLopez, A.-
dc.identifier.citationBlood, 2009; 114(7):1289-1298-
dc.description.abstractAlready 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.-
dc.description.statementofresponsibilityTimothy R. Hercus, Daniel Thomas, Mark A. Guthridge, Paul G. Ekert, Jack King-Scott, Michael W. Parker, and Angel F. Lopez-
dc.publisherAmer Soc Hematology-
dc.rights© 2009 by The American Society of Hematology-
dc.subjectLeukemia, Myeloid-
dc.subjectAcute Disease-
dc.subjectChronic Disease-
dc.subjectReceptors, Granulocyte-Macrophage Colony-Stimulating Factor-
dc.subjectSignal Transduction-
dc.subjectCell Differentiation-
dc.subjectCell Proliferation-
dc.subjectCell Survival-
dc.subjectStructure-Activity Relationship-
dc.titleThe granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease-
dc.typeJournal article-
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]-
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