Oligomerization of the soluble granulocyte-macrophage colony-stimulating factor receptor: Identification of the functional ligand-binding species

被引:10
作者
Brown, CB [1 ]
Pihl, CE [1 ]
Murray, EW [1 ]
机构
[1] UNIV CALGARY,DEPT ONCOL,CALGARY,AB T2N 4N1,CANADA
基金
英国医学研究理事会;
关键词
cytokine; GM-CSF; receptors; soluble;
D O I
10.1006/cyto.1996.0157
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The ligand-specific alpha subunit of the dimeric human GM-CSF receptor exists in both transmembrane anchored (tmGM-CSFR alpha) and soluble (sGM-CSFR alpha) isoforms. sGM-CSFR alpha binds to GM-CSF in solution and antagonizes GM-CSF biological activity in vitro. In an effort to better understand the biological properties of sGM-CSFR alpha the authors have attempted to define the exact stoichiometry of the interaction between GM-CSF and sGM-CSFR alpha. Size separation of sGM-CSFR alpha by polyacrylamide gel electrophoresis (PAGE) under non-reducing conditions demonstrated that sGM-CSFR alpha can exist in solution not only in a monomeric state but also in higher order oligomers, FPLC analysis of ligand/sGM-CSFR alpha complexes suggested that only one of these sGM-CSFR alpha species could functionally bind GM-CSF. PACE analysis of FPLC fractions demonstrated that the peak of GM-CSF binding activity corresponded to the presence of a monomeric form of sCM-CSFR alpha. The experiments demonstrate that while sCM-CSFR alpha can adopt oligomeric forms in solution, the binding of GM-CSF to sGM-CSFR alpha most likely occurs in a (GM-CSF)(1) (sCM-CSFR alpha)(1) configuration. (C) 1997 Academic Press Limited.
引用
收藏
页码:219 / 225
页数:7
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