This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.106.090084v1 92/10/3425    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bardwell, L. Articles by Komarova, N. L. Search for Related Content PubMed PubMed Citation Articles by Bardwell, L. Articles by Komarova, N. L.

Mathematical Models of Specificity in Cell Signaling

Lee Bardwell ^*, Xiufen Zou  , Qing Nie  and Natalia L. Komarova  

^* Department of Developmental and Cell Biology, Department of Mathematics, and Department of Ecology and Evolutionary Biology, University of California-Irvine, Irvine, California USA; and College of Mathematics and Statistics, Wuhan University, Wuhan, China

Correspondence: Address reprint requests to Associate Professor Lee Bardwell, Dept. of Developmental and Cell Biology, 5205 McGaugh Hall, University of California, Irvine, CA 92697-2300. Tel.: 949-824-6902; Fax: 949-824-4709; E-mail: bardwell{at}uci.edu; or Associate Professor Natalia Komarova, Dept. of Mathematics, University of California, Irvine, CA 92697-3875. Tel.: 949-824-1268; Fax: 949-824-7993; E-mail: komarova{at}uci.edu.

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.

This article has been cited by other articles:

				X.-M. Zhao, R.-S. Wang, L. Chen, and K. Aihara Uncovering signal transduction networks from high-throughput data by integer linear programming Nucleic Acids Res., May 1, 2008; 36(9): e48 - e48. [Abstract] [Full Text] [PDF]

				B. D. Slaughter, J. W. Schwartz, and R. Li Mapping dynamic protein interactions in MAP kinase signaling using live-cell fluorescence fluctuation spectroscopy and imaging PNAS, December 18, 2007; 104(51): 20320 - 20325. [Abstract] [Full Text] [PDF]