Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 14 March 2008:
Vol. 319. no. 5869, pp. 1539 - 1543
DOI: 10.1126/science.1151153
Prev | Table of Contents | Next

Reports

Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics

Caleb J. Bashor,1,2 Noah C. Helman,1 Shude Yan,1 Wendell A. Lim1*

Scaffold proteins link signaling molecules into linear pathways by physically assembling them into complexes. Scaffolds may also have a higher-order role as signal-processing hubs, serving as the target of feedback loops that optimize signaling amplitude and timing. We demonstrate that the Ste5 scaffold protein can be used as a platform to systematically reshape output of the yeast mating MAP kinase pathway. We constructed synthetic positive- and negative-feedback loops by dynamically regulating recruitment of pathway modulators to an artificial binding site on Ste5. These engineered circuits yielded diverse behaviors: ultrasensitive dose response, accelerated or delayed response times, and tunable adaptation. Protein scaffolds provide a flexible platform for reprogramming cellular responses and could be exploited to engineer cells with novel therapeutic and biotechnological functions.

1 Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
2 Graduate Group in Biophysics, University of California at San Francisco, 600 16th Street, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: lim{at}cmp.ucsf.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A genetic timer through noise-induced stabilization of an unstable state.
M. Turcotte, J. Garcia-Ojalvo, and G. M. Suel (2008)
PNAS 105, 15732-15737
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)