Biochemical Society Transactions · 2005 · 10 citations · 6 references
Life SciencesImmunologyMolecular BiologyGene ExpressionInnate ImmunitySignal TransductionCell Signaling NetworksCytokine BiologyInflammatory SignalingInnate Immune ResponseInnate Immune Signaling PathwaysToll-like ReceptorsHigh-throughput Functional ScreeningRecombinant Protein PurificationSignal Transduction MechanismsToll-like Receptor SignalingToll-like Receptor Signaling PathwaysToll-like Receptor-mediated Cytokine InductionToll-like Receptor-mediated Innate Immune ResponseToll-like Receptors In Inflammation
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.
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