A connector of two-component regulatory systems promotes signal amplification and persistence of expression

Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St. Louis, MO 63110

Edited by Susan Gottesman, National Institutes of Health, Bethesda, MD, and approved June 4, 2007 (received for review May 11, 2007)

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.

Footnotes

*To whom correspondence should be addressed. E-mail: groisman{at}borcim.wustl.edu
Author contributions: A.K. and A.Y.M. contributed equally to this work; A.K., A.Y.M., and E.A.G. designed research; A.K. and A.Y.M. performed research; A.K., A.Y.M., and E.A.G. analyzed data; and A.K., A.Y.M., and E.A.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0704462104/DC1.
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