Clarification of the role of N-glycans on the common beta-subunit of the human IL-3, IL-5 and GM-CSF receptors and the murine IL-3 beta-receptor in ligand-binding and receptor activation
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Murphy, James; Soboleva, Tatiana; Mirza, Shamaruh; Ford, Sally; Olsen, Jane; Chen, Jinglong; Young, Ian
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Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 are related cytokines that play key roles in regulating the differentiation, proliferation, survival and activation of myeloid blood cells. The cell surface receptors for these cytokines are composed of cytokine-specific α-subunits and a common β-receptor (βc), a shared subunit that is essential for receptor signaling in response to GM-CSF, IL-3 and IL-5. Previous studies have reached conflicting conclusions...[Show more]
dc.contributor.author | Murphy, James | |
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dc.contributor.author | Soboleva, Tatiana | |
dc.contributor.author | Mirza, Shamaruh | |
dc.contributor.author | Ford, Sally | |
dc.contributor.author | Olsen, Jane | |
dc.contributor.author | Chen, Jinglong | |
dc.contributor.author | Young, Ian | |
dc.date.accessioned | 2015-12-08T22:25:10Z | |
dc.identifier.issn | 1043-4666 | |
dc.identifier.uri | http://hdl.handle.net/1885/33320 | |
dc.description.abstract | Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 are related cytokines that play key roles in regulating the differentiation, proliferation, survival and activation of myeloid blood cells. The cell surface receptors for these cytokines are composed of cytokine-specific α-subunits and a common β-receptor (βc), a shared subunit that is essential for receptor signaling in response to GM-CSF, IL-3 and IL-5. Previous studies have reached conflicting conclusions as to whether N-glycosylation of the βc-subunit is necessary for functional GM-CSF, IL-3 and IL-5 receptors. We sought to clarify whether βc N-glycosylation plays a role in receptor function, since all structural studies of human βc to date have utilized recombinant protein lacking N-glycosylation at Asn328. Here, by eliminating individual N-glycans in human βc and the related murine homolog, βIL-3, we demonstrate unequivocally that ligand-binding and receptor activation are not critically dependent on individual N-glycosylation sites within the β-subunit although the data do not preclude the possibility that N-glycans may exert some sort of fine control. These studies support the biological relevance of the X-ray crystal structures of the human βc domain 4 and the complete ectodomain, both of which lack N-glycosylation at Asn328. | |
dc.publisher | Academic Press | |
dc.source | Cytokine | |
dc.subject | Keywords: cytokine receptor; glycan; granulocyte macrophage colony stimulating factor receptor; interleukin 3 beta receptor; interleukin 3 receptor; interleukin 5 receptor; animal cell; article; beta chain; controlled study; crystal structure; glycosylation; ligand ßc; ßIL-3; Cytokine receptor; Interleukin; N-linked glycosylation | |
dc.title | Clarification of the role of N-glycans on the common beta-subunit of the human IL-3, IL-5 and GM-CSF receptors and the murine IL-3 beta-receptor in ligand-binding and receptor activation | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 42 | |
dc.date.issued | 2008 | |
local.identifier.absfor | 060111 - Signal Transduction | |
local.identifier.ariespublication | u4020362xPUB101 | |
local.type.status | Published Version | |
local.contributor.affiliation | Murphy, James, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Soboleva, Tatiana, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Mirza, Shamaruh, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Ford, Sally, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Olsen, Jane, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Chen, Jinglong, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Young, Ian, College of Medicine, Biology and Environment, ANU | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.issue | 2 | |
local.bibliographicCitation.startpage | 234 | |
local.bibliographicCitation.lastpage | 42 | |
local.identifier.doi | 10.1016/j.cyto.2008.02.010 | |
dc.date.updated | 2015-12-08T09:03:31Z | |
local.identifier.scopusID | 2-s2.0-43049175033 | |
local.identifier.thomsonID | 000256535700012 | |
Collections | ANU Research Publications |
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