Abstract:
:Cell signaling systems sense and respond to ligands that bind cell surface receptors. These systems often respond to changes in the concentration of extracellular ligand more rapidly than the ligand equilibrates with its receptor. We demonstrate, by modeling and experiment, a general "systems level" mechanism cells use to take advantage of the information present in the early signal, before receptor binding reaches a new steady state. This mechanism, pre-equilibrium sensing and signaling (PRESS), operates in signaling systems in which the kinetics of ligand-receptor binding are slower than the downstream signaling steps, and it typically involves transient activation of a downstream step. In the systems where it operates, PRESS expands and shifts the input dynamic range, allowing cells to make different responses to ligand concentrations so high as to be otherwise indistinguishable. Specifically, we show that PRESS applies to the yeast directional polarization in response to pheromone gradients. Consideration of preexisting kinetic data for ligand-receptor interactions suggests that PRESS operates in many cell signaling systems throughout biology. The same mechanism may also operate at other levels in signaling systems in which a slow activation step couples to a faster downstream step.
journal_name
Proc Natl Acad Sci U S Aauthors
Ventura AC,Bush A,Vasen G,Goldín MA,Burkinshaw B,Bhattacharjee N,Folch A,Brent R,Chernomoretz A,Colman-Lerner Adoi
10.1073/pnas.1322761111subject
Has Abstractpub_date
2014-09-16 00:00:00pages
E3860-9issue
37eissn
0027-8424issn
1091-6490pii
1322761111journal_volume
111pub_type
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