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Functional mapping of Toll/interleukin-1 signalling networks by expression cloning
E Kiss-Toth1, D H Wyllie, K Holland
1Cardiovascular Research Unit, University of Sheffield, Sheffield, UK. e.kiss-toth@sheffield.ac.uk
Biochemical Society Transactions
|October 26, 2005
Summary
Researchers developed a high-throughput screening platform to identify proteins involved in inflammatory gene expression. This new method helps map complex cellular signaling networks and estimate the number of gene products regulating key inflammatory genes.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Toll/interleukin-1 receptor (TIR) signaling pathways regulate inflammatory gene expression.
- Numerous cellular proteins participate in TIR-mediated inflammation, but many signaling network components remain unidentified.
- Current methods for identifying novel components include sequence similarity, protein-protein interactions, and protein purification.
Purpose of the Study:
- To develop a high-throughput functional screening platform for identifying components of inflammatory signaling networks.
- To apply this platform to identify novel components involved in Toll/interleukin-1 receptor-mediated inflammatory gene expression.
- To estimate the number of gene products controlling the transcription of the human interleukin 8 gene.
Main Methods:
- Development of a high-throughput functional screening platform.
- Application of the platform to map inflammatory signaling networks.
- Utilizing the platform to identify novel signaling components controlling gene expression.
Main Results:
- Successfully developed and applied a simple, robust high-throughput functional screening platform.
- Identified numerous components within inflammatory signaling networks.
- Estimated that 100-150 gene products control the transcription of the human interleukin 8 gene.
Conclusions:
- The developed platform is a general and efficient method for mapping signal transduction systems.
- This approach enables the rapid isolation of a large number of signaling components.
- The findings provide new insights into the complexity of inflammatory gene regulation.
