title: An interleukin 5 mutant distinguishes between two functional responses in human eosinophils.
abstract: Interleukin 5 (IL-5) is the key cytokine involved in regulating the production and many of the specialized functions of mature eosinophils including priming, adhesion, and survival. We have generated a point mutant of human IL-5, IL-5 (E12K), which is devoid of agonist activity in both a TF-1 cell proliferation assay and a human eosinophil adhesion assay. However, IL-5 (E12K) is a potent and specific antagonist of both these IL-5-dependent functional responses. In both receptor binding and cross-linking studies the wild-type and IL-5 (E12K) mutant exhibit virtually identical properties. This mutant protein was unable to stimulate tyrosine phosphorylation in human eosinophils, and blocked the phosphorylation stimulated by IL-5. In contrast, IL-5 (E12K) is a full agonist in a human eosinophil survival assay, although with reduced potency compared to the wild-type protein. This IL-5 mutant enables us to clearly distinguish between two IL-5-dependent functional responses and reveals distinct mechanisms of receptor/cellular activation.
authors.affiliation: Cell Biology Unit, GlaxoWellcome Research and Development, Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: McKinnon
authors.forename: K
authors.initials: K
authors.lastname: Page
authors.forename: I J
authors.initials: IJ
authors.lastname: Uings
authors.forename: M
authors.initials: M
authors.lastname: Banks
authors.forename: D
authors.initials: D
authors.lastname: Fattah
authors.forename: A E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: P
authors.initials: P
authors.lastname: Graber
authors.forename: C
authors.initials: C
authors.lastname: Arod
authors.forename: R
authors.initials: R
authors.lastname: Fish
authors.forename: T N
authors.initials: TN
authors.lastname: Wells
authors.forename: R
authors.initials: R
authors.lastname: Solari
mesh_terms: D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D018123:Receptors, Interleukin / Q000276:immunology; D053649:Receptors, Interleukin-5; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5