Signal duration and the time scale dependence of signal integration in biochemical pathways
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA
Department of Systems Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston MA 02115, USA
BMC Systems Biology 2008, 2:108 doi:10.1186/1752-0509-2-108Published: 17 December 2008
Signal duration (e.g. the time over which an active signaling intermediate persists) is a key regulator of biological decisions in myriad contexts such as cell growth, proliferation, and developmental lineage commitments. Accompanying differences in signal duration are numerous downstream biological processes that require multiple steps of biochemical regulation.
Here we present an analysis that investigates how simple biochemical motifs that involve multiple stages of regulation can be constructed to differentially process signals that persist at different time scales. We compute the dynamic, frequency dependent gain within these networks and resulting power spectra to better understand how biochemical networks can integrate signals at different time scales. We identify topological features of these networks that allow for different frequency dependent signal processing properties.
We show that multi-staged cascades are effective in integrating signals of long duration whereas multi-staged cascades that operate in the presence of negative feedback are effective in integrating signals of short duration. Our studies suggest principles for why signal duration in connection with multiple steps of downstream regulation is a ubiquitous motif in biochemical systems.