Functional mapping of Toll/interleukin-1 signalling networks by expression cloning.
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.
Kiss-Toth
E
E
Cardiovascular Research Unit, University of Sheffield, Sheffield, UK. e.kiss-toth@sheffield.ac.uk
Wyllie
D H
DH
Holland
K
K
Marsden
L
L
Jozsa
V
V
Oxley
K M
KM
Polgar
T
T
Qwarnstrom
E E
EE
Dower
S K
SK
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*
D007375:Interleukin-1; D016209:Interleukin-8; D051193:Toll-Like Receptors