Journal article
Slow-dissociation effect of common signaling subunit β on IL5 and GM-CSF receptor assembly
Cytokine (Philadelphia, Pa.), v 42(2), pp 179-190
May 2008
PMID: 18294864
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Receptor activation by IL5 and GM-CSF is a sequential process that depends on their interaction with a cytokine-specific subunit α and recruitment of a common signaling subunit β (βc). In order to elucidate the assembly dynamics of these receptor subunits, we performed kinetic interaction analysis of the cytokine–receptor complex formation by a surface plasmon resonance biosensor. Using the extracellular domains of receptor fused with C-terminal V5-tag, we developed an assay method to co-anchor α and βc subunits on the biosensor surface. We demonstrated that dissociation of the cytokine–receptor complexes was slower when both subunits were co-anchored on the biosensor surface than when α subunit alone was anchored. The slow-dissociation effect of βc had a similar impact on GM-CSF receptor stabilization to that of IL5. The effects were abolished by alanine replacement of either Tyr18 or Tyr344 residue in βc, which together constitute key parts of a cytokine binding epitope. The data argue that βc plays an important role in preventing the ligand–receptor complexes from rapidly dissociating. This slow-dissociation effect of βc explains how, when multiple βc cytokine receptor α subunits are present on the same cell surface, selective βc usage can be controlled by sequestration in stabilized cytokine–α–βc complexes.
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Details
- Title
- Slow-dissociation effect of common signaling subunit β on IL5 and GM-CSF receptor assembly
- Creators
- Tetsuya IshinoAdrian E HarringtonMeirav Zaks-ZilbermanJeffery J ScibekIrwin Chaiken
- Publication Details
- Cytokine (Philadelphia, Pa.), v 42(2), pp 179-190
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000256535700006
- Scopus ID
- 2-s2.0-43149117024
- Other Identifier
- 991014878220304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Immunology