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

Barbara J. McClure, Joanna M. Woodcock, Duygu Harrison-Findik, Angel F. Lopez, Richard J. D'Andrea

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The 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, hβc. We generated a chimeric cytokine receptor in which the extracellular and transmembrane domains of hilt 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 α-subunit, the hβc-EPO receptor chimera transduces a mitogenic signal in BaF-B03 in response to GM-CSF. This is consistent with formation of a hβc homodimer following GM-CSF binding and implies that ligand stimulation induces formation of a higher order complex that contains the hβc homodimer.

Original languageEnglish (US)
Pages (from-to)240-243
Number of pages4
JournalCytokine
Volume13
Issue number4
DOIs
StatePublished - Feb 21 2001

Fingerprint

Oligomerization
Granulocyte-Macrophage Colony-Stimulating Factor
Erythropoietin Receptors
Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Cytokine Receptors
Dimerization
Stoichiometry
Assays
Chemical activation
Ligands

Keywords

  • Cytokine receptor
  • Erythropoietin
  • GM-CSF
  • Signalling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

McClure, B. J., Woodcock, J. M., Harrison-Findik, D., Lopez, A. F., & D'Andrea, R. J. (2001). GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit. Cytokine, 13(4), 240-243. https://doi.org/10.1006/cyto.2000.0826

GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit. / McClure, Barbara J.; Woodcock, Joanna M.; Harrison-Findik, Duygu; Lopez, Angel F.; D'Andrea, Richard J.

In: Cytokine, Vol. 13, No. 4, 21.02.2001, p. 240-243.

Research output: Contribution to journalArticle

McClure, BJ, Woodcock, JM, Harrison-Findik, D, Lopez, AF & D'Andrea, RJ 2001, 'GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit', Cytokine, vol. 13, no. 4, pp. 240-243. https://doi.org/10.1006/cyto.2000.0826
McClure BJ, Woodcock JM, Harrison-Findik D, Lopez AF, D'Andrea RJ. GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit. Cytokine. 2001 Feb 21;13(4):240-243. https://doi.org/10.1006/cyto.2000.0826
McClure, Barbara J. ; Woodcock, Joanna M. ; Harrison-Findik, Duygu ; Lopez, Angel F. ; D'Andrea, Richard J. / GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit. In: Cytokine. 2001 ; Vol. 13, No. 4. pp. 240-243.
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