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PNAS 105 (20): 7165-7170

Copyright © 2008 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / BIOPHYSICS

Signal processing by the HOG MAP kinase pathway

Pascal Hersen{dagger},{ddagger}, Megan N. McClean{dagger},§, L. Mahadevan§, and Sharad Ramanathan{dagger},¶,||

{dagger}FAS Center for Systems Biology and §School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; {ddagger}Laboratoire Matière et Systèmes Complexes, Centre National de la Recherche Scientifique and Université Paris Diderot, 75205 Paris Cedex 13, France; and Bell Laboratories, Alcatel–Lucent, Murray Hill, NJ 07974

Edited by Charles F. Stevens, Salk Institute for Biological Studies, La Jolla, CA, and approved February 29, 2008

Received for publication November 13, 2007.

Abstract: Signaling pathways relay information about changes in the external environment so that cells can respond appropriately. How much information a pathway can carry depends on its bandwidth. We designed a microfluidic device to reliably change the environment of single cells over a range of frequencies. Using this device, we measured the bandwidth of the Saccharomyces cerevisiae signaling pathway that responds to high osmolarity. This prototypical pathway, the HOG pathway, is shown to act as a low-pass filter, integrating the signal when it changes rapidly and following it faithfully when it changes more slowly. We study the dependence of the pathway's bandwidth on its architecture. We measure previously unknown bounds on all of the in vivo reaction rates acting in this pathway. We find that the two-component Ssk1 branch of this pathway is capable of fast signal integration, whereas the kinase Ste11 branch is not. Our experimental techniques can be applied to other signaling pathways, allowing the measurement of their in vivo kinetics and the quantification of their information capacity.

Key Words: bandwidth • HOG pathway • microfluidics • signal transduction

Freely available online through the PNAS open access option.

Author contributions: P.H. and M.N.M. contributed equally to this work; P.H., M.N.M., L.M., and S.R. designed research; P.H. and M.N.M. performed research; P.H. and M.N.M. contributed new reagents/analytic tools; P.H., M.N.M., and S.R. analyzed data; and P.H., M.N.M., and S.R. 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/0710770105/DCSupplemental.

||To whom correspondence should be addressed at: 206 Bauer Center, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138. E-mail: sharad{at}post.harvard.edu

© 2008 by The National Academy of Sciences of the USA

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