title: Feedback loops in intracellular signal processing and their potential for identifying novel signalling proteins.
abstract: Mapping of intracellular signalling networks has attracted a lot of attention during recent years. Approaches which have been used to characterise functional and physical relationships within signalling systems and to identify novel components have included bioinformatics, genomics, proteomics and genetics. However, the importance of feedback loops in the regulation of signal processing systems has often been ignored. Here we report a novel focus for our previous screening platform, which evaluates the potential of autocatalytic feedback for functional screening of cDNA expression libraries. We confirm that the use of such systems is feasible. We propose that the use of feedback loops in functional screens may introduce a bias towards the detection of signalling molecules, which are likely to be of key regulatory importance due to the sensitivity of the system towards their expression levels.
authors.affiliation: Academic Unit of Cell Biology, Sheffield S10 2JF, United Kingdom.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Guan
authors.forename: Karen
authors.initials: K
authors.lastname: Holland
authors.forename: Eva
authors.initials: E
authors.lastname: Qwarnstrom
authors.forename: Steven K
authors.initials: SK
authors.lastname: Dower
authors.forename: Endre
authors.initials: E
authors.lastname: Kiss-Toth
mesh_terms: D025461:Feedback, Physiological; D015723:Gene Library; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D049452:Green Fluorescent Proteins