title: Functional mapping of Toll/interleukin-1 signalling networks by expression cloning.
abstract: Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein-protein interactions and protein purification, suggests that many elements of this signalling network remain to be identified. We report here the development of a high-throughput functional screening platform and its application for the identification of components of inflammatory signalling networks. Our results enable us to estimate that 100-150 gene products are involved in controlling the transcription of the human interleukin 8 gene. The approach, which is simple and robust, constitutes a general method for mapping signal transduction systems and for rapid isolation of a large number of signalling components based on the control of pathways leading to regulation of gene expression.
authors.affiliation: Cardiovascular Research Unit, University of Sheffield, Sheffield, UK. e.kiss-toth@sheffield.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Kiss-Toth
authors.forename: D H
authors.initials: DH
authors.lastname: Wyllie
authors.forename: K
authors.initials: K
authors.lastname: Holland
authors.forename: L
authors.initials: L
authors.lastname: Marsden
authors.forename: V
authors.initials: V
authors.lastname: Jozsa
authors.forename: K M
authors.initials: KM
authors.lastname: Oxley
authors.forename: T
authors.initials: T
authors.lastname: Polgar
authors.forename: E E
authors.initials: EE
authors.lastname: Qwarnstrom
authors.forename: S K
authors.initials: SK
authors.lastname: Dower
mesh_terms: D003001:Cloning, Molecular / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D051193:Toll-Like Receptors