Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 33, Pages 13307-13312Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0706311104
Keywords
MAPK; mathematical modeling; Monte Carlo simulations; cell signaling; phosphatase activity
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The assembly of multiple signaling proteins into a complex by a scaffold protein guides many cellular decisions. Despite recent advances, the overarching principles that govern scaffold function are not well understood. We carried out a computational study using kinetic Monte Carlo simulations to understand how spatial localization of kinases on a scaffold may regulate signaling under different physiological conditions. Our studies identify regulatory properties of scaffold proteins that allow them to both amplify and attenuate incoming signals in different biological contexts. These properties are not caused by the well established prozone or combinatorial inhibition effect. These results bring coherence to seemingly paradoxical observations and suggest that cells have evolved design rules that enable scaffold proteins to regulate widely disparate cellular functions.
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