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Biophys. J. BioFAST: First Published February 26, 2007. doi:10.1529/biophysj.106.090084
© 2007 by the Biophysical Society.

A more recent version of this article appeared on May 15, 2007.
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BIOPHYSICAL THEORY AND MODELING

Mathematical Models of Specificity in Cell Signaling

Lee Bardwell 1*, Xiufen Zou 2, Qing Nie 1 and Natalia L Komarova 1

1 University of California, Irvine
2 Wuhan University

* To whom correspondence should be addressed. E-mail: bardwell{at}uci.edu.

Submitted on May 30, 2006
Revised on July 21, 2006
Accepted on 17 January 2007


  Abstract
Cellular signaling pathways transduce extracellular signals into appropriate responses. These pathways are typically interconnected to form networks, often with different pathways sharing similar or identical components. A consequence of this connectedness is the potential for cross-talk, some of which may be undesirable. Indeed, experimental evidence indicates that cells have evolved insulating mechanisms to partially suppress 'leaking' between pathways. Here we characterize mathematical models of simple signaling networks and obtain exact analytical expressions for two measures of cross-talk called specificity and fidelity. The performance of several insulating mechanisms -combinatorial signaling, compartmentalization, the inhibition of one pathway by another, and the selective activation of scaffold proteins- is evaluated with respect to the trade-off between the specificity they provide and the constraints they place on the network. The effects of noise are also examined. The insights gained from this analysis are applied to understanding specificity in the yeast mating and invasive growth MAP kinase signaling network.

Key Words: Ste5 Fus3 Tec1, mathematical model, network, protein kinase, scaffold protein, signal transduction




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Copyright © 2007 by the Biophysical Society.