title: In vitro characterization of the human recombinant soluble granulocyte-macrophage colony-stimulating factor receptor.
abstract: We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF.
authors.affiliation: Department of Medicine, University of Calgary, Alberta, Canada.
authors.forename: C B
authors.initials: CB
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Beaudry
authors.forename: T D
authors.initials: TD
authors.lastname: Laing
authors.forename: S
authors.initials: S
authors.lastname: Shoemaker
authors.forename: K
authors.initials: K
authors.lastname: Kaushansky
mesh_terms: D001667:Binding, Competitive; D006031:Glycosylation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor