INVESTIGADORES
COLMAN LERNER Alejandro Ariel
artículos
Título:
Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range
Autor/es:
ALEJANDRA VENTURA; ALAN BUSH; GUSTAVO VASEN; MATÍAS GOLDÍN; BRIANNE BURKINSHAW; NIRVEEK BHATTACHARJEE; ALBERT FOLCH; ROGER BRENT; ARIEL CHERNOMORETZ; ALEJANDRO COLMAN LERNER
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2014
ISSN:
0027-8424
Resumen:
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 sys- tems 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 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 gra- dients. 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.