GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit

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dc.contributor.authorMc Clure, B.
dc.contributor.authorWoodcock, J.
dc.contributor.authorHarrison-Findik, D.
dc.contributor.authorLopez, A.
dc.contributor.authorD'Andrea, R.
dc.date.issued2001
dc.description.abstractThe stoichiometry of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor complex is still unresolved. We have utilised a sensitive, functional assay for receptor homodimerisation to show that GM-CSF induces dimerisation of the common signalling subunit, hbeta(c). We generated a chimeric cytokine receptor in which the extracellular and transmembrane domains of hbeta(c)are fused to the cytoplasmic domain of erythropoietin receptor (EPO-R). Given that to induce EPO-R activation and mitogenic signalling there is a requirement for formation of a specific homodimeric complex, we reasoned that the cytoplasmic domain of EPO-R could be utilised as a highly sensitive reporter for functional homodimer formation. We show that, in the presence of a cytoplasmically truncated GM-CSF alpha-subunit, the hbetac-EPO receptor chimera transduces a mitogenic signal in BaF-B03 in response to GM-CSF. This is consistent with formation of a hbeta(c)homodimer following GM-CSF binding and implies that ligand stimulation induces formation of a higher order complex that contains the hbeta(c)homodimer.
dc.identifier.citationCytokine, 2001; 13(4):240-243
dc.identifier.doi10.1006/cyto.2000.0826
dc.identifier.issn1043-4666
dc.identifier.issn1096-0023
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]
dc.identifier.urihttp://hdl.handle.net/2440/9391
dc.language.isoen
dc.publisherAcadmic Press
dc.source.urihttps://doi.org/10.1006/cyto.2000.0826
dc.subjectCell Line
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectGranulocyte-Macrophage Colony-Stimulating Factor
dc.subjectReceptors, Cell Surface
dc.subjectReceptors, Granulocyte-Macrophage Colony-Stimulating Factor
dc.subjectRecombinant Fusion Proteins
dc.subjectSignal Transduction
dc.subjectProtein Binding
dc.subjectDimerization
dc.subjectCytokine Receptor Common beta Subunit
dc.titleGM-CSF binding to its receptor induces oligomerisation of the common beta-subunit
dc.typeJournal article
pubs.publication-statusPublished

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