Biphasic regulation in biological processes: the mechanisms and physiological roles

22 April 2005

Andre Levchenko
Signal Transduction and Cell-Cell Communication Lab
Whittaker Institute of Biomedical Engineering
Johns Hopkins University


Biphasic regulation is defined here as the ability of diverse biological systems to respond optimally (maximally) to a given input, with response reducing if the input deviates from this particular value. The overall response can thus be 'bell shaped', often symmetric in semi-log coordinates. Here I will characterize three classes of mechanisms generating biphasic response in biology and discuss their respective properties. In addition, using examples of our own research into scaffolds in MAPK pathways, cross-talk in calcineurin pathway, calcium regulation, and quorum sensing in bacteria, I will discuss the particular physiological instances of biphasic regulation and its use in implementaion of a range of biological functions.


A Levchenko, J Bruck, P W Sternberg, "Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties", PNAS 97:5818-23 2000. PubMed.

A Levchenko, J Bruck, P W Sternberg, "Regulatory modules that generate biphasic signal response in biological systems", IEE Systems Biology 1:139-148, 2004. PDF.

Z Hilioti et al, "GSK-3 kinases enhance calcineurin signalling by phosphorylation of RCNs", Genes & Development 18:35-47 2004. PubMed. PDF.

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