title: A connector of two-component regulatory systems promotes signal amplification and persistence of expression.
abstract: Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect two-component regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification.
authors.affiliation: Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Akinori
authors.initials: A
authors.lastname: Kato
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Mitrophanov
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D007700:Kinetics; D008957:Models, Genetic; D011112:Polymyxin B / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019779:Salmonella enterica / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; C087732:PmrD protein, Salmonella; D012333:RNA, Messenger; C081902:pmrA protein, Bacteria; C061064:PhoP protein, Bacteria; D011112:Polymyxin B