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Science 310 (5747): 496-498

Copyright © 2005 by the American Association for the Advancement of Science

Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions

Onn Brandman,1,2* James E. Ferrell, Jr.,1 Rong Li,2,3,4 Tobias Meyer1,2

Abstract: Positive feedback is a ubiquitous signal transduction motif that allows systems to convert graded inputs into decisive, all-or-none outputs. Here we investigate why the positive feedback switches that regulate polarization of budding yeast, calcium signaling, Xenopus oocyte maturation, and various other processes use multiple interlinked loops rather than single positive feedback loops. Mathematical simulations revealed that linking fast and slow positive feedback loops creates a "dual-time" switch that is both rapidly inducible and resistant to noise in the upstream signaling system.

1 Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
2 Physiology Course 2004, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
3 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
4 The Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

* To whom correspondence should be addressed. E-mail: onn{at}

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